Bones and Joints

Question 1

Describe the anatomy of normal bone

Answer 1

Question 2

What is osteomyelitis?

Answer 2

• Bone infected with microorganisms

  -> Inflammation of entire bone
  
-> Acute inflammation, tissue necrosis
• Bone infection through usually through S. aureus:
  
 - Spread through the bloodstream into the bone
  
 - Open fracture or surgery
• Symptoms: pain, fever, chills
• Predisposing factors:
 Fractures due to trauma, uncontrolled diabetes, radiation damage, Paget’s disease, Osteoporosis


Aetiology: Staph aureus (80-90%), E.coli & others
- Haematogenous spread

- Extension from nearby site

- Direct implantation


Pathogenesis:

- Bacteria enter the bone
 -> Proliferate in areas of lowest blood supply 

- children - distal femur and proximal tibia

- adults - axial skeleton

- Eventually fibrous tissue and reactive bone is laid down
- Involucrum = layer of new bone growth outside existing dead bone

Question 3

What is Paget’s Disease?

Answer 3

• Caused by excessive breakdown (osteoclasts) and formation of bone (osteoblasts), followed by disorganized bone remodeling -> imbalance between osteoclast and osteoblast function
• New bone is often weak and brittle -> breaks easily
  
- Bone pain due to microfractures
• Most commonly in axial skeleton or proximal femur (80%)
• People > 50 years of age
• Aetiology unknown but infection and genetic factors
• Treatmentcalcitonin (decreases blood calcium levels)













Pathogenesis consists of 3 phases:

1. Osteolytic stage: furious bone resorption by osteoclasts

2. Mixed stage (lytic and blastic): hectic bone formation by osteoblasts but a in disorganised manner

3. Osteosclerotic stage: “burnt out” with disordered and structurally unsound hyper-dense bone

Question 4

What is osteoarthritis?

Answer 4

• -itis usually implies inflammatory disease but is actually primarily a degenerative disease of articular cartilage
• Normal occurrence with age
  
- affects 14% of adults aged 25 years and older (US)

  
  • affects 34% of those over 65 years and older (US)
• Has genetic predisposition
• Imbalance in expression, activity and signaling of cytokines and growth factors -> degeneration and loss of matrix
• Joints of hands, knee, hip, spine most often affected
• Symptoms: pain, aching, stiffness and swelling in and around one or more joints

Question 5

What is rheumatoid arthritis (RA) and its pathogenesis?

Answer 5

• Systemic, chronic inflammatory autoimmune disease
• Affects many organs but principally attacks joints
• Prevalence in women is 2-4 x higher
• Extensive synovial hyperplasia and infiltration by lymphocytes, monocytes, macrophages, and fibroblasts
• Non-suppurative proliferative synovitis -> frequently progresses to destroy articular cartilage and underlying bone
• Predominantly CD4+T helper type 1 (Th1)-driven disease
• Genetic predisposition (HLA-DRB1)
• Epstein Barr virus association -> high Ab titers against EBV antigens in RA
• Blood of >70% of patients contains anti-CCP (cyclic citrullinated peptide) autoantibodies

Pathogenesis (joint RA):

- B cells (rheumatoid factor) and T cells involved in an immune reaction

- CD4+ T cells stimulate cytokine release

- Cytokines (IL-1 & TNF) stimulate:

- Synovial cell proliferation

- Cartilage destruction

- Osteoclast stimulation and bone destruction
- Hyperplastic synovium grows over articulating surface forming an invasive “pannus” -> irreversible cartilage destruction and erosion of bone


Question 6

What is the anatomy and morphology of pannus?

Answer 6

Question 7

What is the difference between rheumatoid arthritis and osteoarthritis?

Answer 7

Question 8

What is gout and its pathology?

Answer 8

• Rheumatic disease
• Acute arthritis initiated by urate crystals in and around joints
• Only 5% with hyperuricemia get gout
• In acute form: severely red, hot and swollen joint with agonizing pain
  

  Aetiology: hyperuricemia due to:
  1. Enzyme defects causing overproduction of uric acid

  2. Increased nucleic acid turnover (e.g leukemia)

  3. Reduced uric acid excretion (e.g kidney disease)
  
4. Inborn errors of metabolism (e.g HGPRT deficiency)


Pathogenesis:

- Urate crystals precipitate out of blood and develop in synovium and cartilage

- Trauma of the joint causes release of crystals -> crystals in joint start cascade of inflammation (leukocytes and complement activation)

- Recurrent acute exacerbations lead to chronic arthritis and formation of “tophi”, pannus and severe cartilage damage

Question 9

What is osteoperosis?

Answer 9

• Reduced bone mass/density and increased porosity of skeleton

Aetiology:

- Post menopausal

- Age
- Reduced physical activity

- Endocrine disorders

- Genetics

- Nutritional state

- Medications (steroids)











• Imbalance betweenbone resorptionand bone formation
• Osteoclasts break down bone –> calcium release
• Osteoblasts deposit calcium into bone

Question 10

What is osteogenesis imperfecta?

Answer 10

• Group of disorders caused by deficiency of type 1 collagen
• Mutations in COL1A1 and COL1A2genes which code for collagen type 1
• Autosomal dominant