Week 20 Pathology

Fracture healing

  • Haematoma formation – immediately after fracture occurs. Fills the fracture gap. This provides a fibrin mesh.
  • Inflammation via degranulation of platelets and migration of inflammatory cells eg Neutrophils–> release of PDGF, TGF B which activate osteoprogenitor cells in periosteum and medullary cavity. –> osteoclastic and osteoblastic activity.
  • Haematoma Organising by end of first week – Macrophages
  • Procallus – provides anchorage between the ends but offers no structural integrity for weight bearing.
  • Callus formation – subperiosteal deposition of trabecular woven bone. Maximal girth at week 2-3.
  • Endochondral calcification.
  • Tissue remodelling after weight bearing. Excesses are resorbed



  • Inflammation of bone and marrow. Virtually always infectious.
  • Haematogenous, extension from contiguous site, direct innoculation
  • Long bones or vertebral bodies in healthy people.
  • Staph aureus 80-90%
  • Those with IVDU or genitourinary tract infections –> E Coli, Klebsiella, Pseudomonas.
  • Neonates – GBS and haemophilus influenzae. Metaphysis, epiphysis or both.
  • Childeren – metaphysis
  • Adult – ephiphyses and subchondral regions.
  • Sickle cell – Salmonella
  • Direct innoculation or contiguous spread – mixed organisms.
  • 50% of time no organism identified.


  • Once infection localised –> inflammatory response –> cell death in 1st 48hrs–> after 1st week chronic inflamation cell infiltrate –> osteoclastic bone resorption–> ingrowth of fibrous tissue–> deposition of reactive bone in periphery (involucrum).
  • Children – subperiosteal abscess may form. Lifting the periosteum further.
  • Supparative and ischaemic bone injury –> segmental bone necrosis =sequestrum.
  • 5-25% become chronic infection.


Osteoarthritis OA.

  • Degenerative joint disease characterised by progressive erosion of articular cartilage. Ageing phenomenon. Can be secondary to joint trauma, haemochromatosis etc.
  • Normal cartilage has type 2 collagen and proteoglycans.
  • Causes – mechanical workload, genetics,
  • Characteristics – early – more water and less proteoglycans, less t2 collagen, rise in IL1 and TNF a. Granular articular surface, softer than normal.
  • Chondrocytes in deeper layer proliferate
  • Subchondral bone exposed –> bone eburnation–> sclerosis of underlying bone.
  • Bone cysts from leakage of synovial fluid via small fracture gaps in subchondral bone.
  • Osteophyte formation.
  • Clinical pic – deep achy pain worse with mobilisation, crepitus, stiffness, limit ROM, vertebral osteophytes –> neurological sx.


Rheumatoid Arthritis RA.

  • Chronic systemic inflammatory disorder affecting joints, skin, blood vessels, heart and muscles
  • Nonsupparative proliferative and inflammatory synovitis–> destruction of articular cartilage and ankylosis of joints.
  • 1% of world affected. Women more.
  • Joint synovium – oedema, thickened, and hyperplastic. Perivascular inflammatory cells, B ells, CD4, plasma cells and macrophages. Increased vascularity. Aggregation of fibrin and neutrophils in synovial fluid.
  • Osteoclastic activity –> juxta-articular erosions, subchondral cysts and osteoporosis.
  • Pannus formation.
  • Rh nodules – ulnar aspect of forearm – firm and nontender – central fibrinoid necrosis and surrounding epitheloid histiocytes, lymphocytes and plasma cells.
  • Autoimmune disease triggered by exposure of a genetically susceptible host to an unkown antigen.
  • Proximal small joints, symmetrical. PIP, MCP, MTP, wrist. Stiffness. Better with activity. Deformity.
  • Radiology – juxta-articular osteopenia, bone erosions, narrowing of joint space, destruction of tendons etc.


Septic arthritis.

  • Haematogenous, contiguous spread, direct innoculation
  • Rapid joint destruction and deformity. Systemically unwell. Pain!
  • Gonnococcus(late adolescence and young adults, sexually active women), staphylococcus aureus(main one in older kids and adults), streptococcus, haemophilus influenzae(children under2), GNB. Salmonella(sickle cell)
  • Usually knee followed by hip, shoulder, elbow. IVDU – axial joints. Gonoccocal – multiple joints.


Gout and Pseudogout

Gout Pseudogout
Urate crystal deposits in synovium and cause inflammation via C3, C5, neutrophils, macrophages, chemokines, fibroblasts, Calcium pyrophosphate crystal
Negative refringent Positive refringent
Chronic – tophi, joint deformity, urate nephropathy Sporadic, hereditary (most severe) and secondary.
Usually all primary – unkown genetic defects affecting urate metabolism. Secondary can be due to increased cell turnover eg leukaemia, chronic renal impairment.
Alcohol predisposes to attacks, as does obesity, genetics, drugs eg thiazides

Seronegative arthropathies.

  • T cell response to unknown antigen
  • Ankylosing spondylitis
    • Axial joints esp sacroiliac, men more than women, 90% HLAB27 positive,
    • Chronic synovitis, destruction of articular cartilage, bony ankylosis, inflammation of tendinoligaments –> calcification.
    • Cx – fracure of spine, uveitis, aortitis, amyloidosis.
  • Reactive arthritis/Reiters syn
    • Episode of noninfective arthritis of appendicular skeleton within 1mo of primary infection elsewhere.
    • Usually genitourinary origin or GI – chlamydia, shigella, salmonella, yersinia, campylobacter.
    • Triad – arthritis, nongonnococcal urethritis or cervicitis, conjunctivitis.
    • 80% HLA B27 positive.
    • 50% have recurrent arthritis, tendinitis, fasciitis etc
  • Psoriatic arthritis
    • 10% of patients with psoraisis
    • Distal IP joints of hand and feet first affected, asymmetric,
    • Sausage finger from inflam of digital tendon sheaths.
    • Conjunctivitis, iritis. Joint destruction les frequent, remission more frequent.
  • IBD associated.


Avascular Necrosis – AVN

  • All form of bone necrosis result from ischaemia.
    • Mechanical vascular interruption eg fracture
    • Steroids
    • Thrombosis and embolism
    • Vessel injury due to radiation etc
    • Increased intraosseous pressure with vascular compression
    • Venous hypertension
  • Medullary infarcts. Cortex usually unaffected due to collateral supply. Usually clinically silent.
  • Subchondral infarct – wedge shaped with apex at epiphysis. Causes chronic pain and secondary OA.