Pathology Flashcards
What is the most common degenerative joint disease?
Osteoarthritis
What is the pathogenesis of osteoarthritis?
Chronic progressive destruction of articular cartilage
- can be 1° or 2° (eg. trauma, congenital abnormality, avascular necrosis, other joint disease)
How does osteoarthritis present?
1) Pain
2) Limitation of movements
3) Swelling and osteophytes
4) Cervical spondylosis spinal nerve compression
What are the 3 forms of osteoarthritis?
1) Primary generalised OA
- most common in post-menopausal women
2) Erosive inflammatory OA
- severe destructive disease w rapid progression
3) Hypertrophic OA
- florid osteophyte formation, bone sclerosis w slow progression
What is the pathogenesis of hypertrophic osteoarthritis?
Multifactoral
eg. ↑joint load
degradation of articular cartilage
biochemical abnormalities (eg. ↓proteoglycans, protein synthesis, chondrocyte replication)
Genetic abnormalities (familial mutation of type 2 collage COL2A1)
Degenerative, inflammatory and reparative activity involving articular cartilage & subarticular bone, with secondary effects on synovium, muscle and nerves.
What is the characteristic histological findings in osteoarthritis?
Damage and destruction of articular cartilage:
- thinning
- erosion
- fibrillation/erosion → “cracking”
What are 2 bone presentations of osteoarthritis?
1) Eburnation
- exposed bone w polished surface due to contact friction of bone surface
2) Formation of subchondral cyst
3) Thickening of subarticular bone
What are 4 radiological features of osteoarthritis?
1) Narrowing of the joint space
2) Sclerosis (thickening of subchondral bone)
3) Subchondral cyst
4) Osteophytes (peripheral growths of bone and cartilage)
What are 5 pathological findings of osteoarthritis?
1) Destruction of articular cartilage
2) Eburnation and thickening of subarticular bone
3) Formation of subchondral cyst
4) Formation of osteophytes/bone (eg. Herberden’s nodes)
5) Reactive thickening of synovium
6) Secondary changes to surrounding tissue (eg. muscle atrophy)
What is the normal structure of an intervertebral disc?
1) Central nucleus pulposus (water, proteoglycans)
2) Surrounding annulus of obliquely oriented collagen fibres
3) Cartilaginous end plate
What are 4 possible aetiologies/components of intervertebral disc degeneration?
1) Genetics
2) Age-related “wear and tear”
- eg. nucleus pulposus becomes dehydrated, fibrotic and atrophied
3) Mechanical
- eg. occupational, bad posture, strain, trauma → crack/tears in disc annulus and nucleus pulposus
4) Others
- eg. nutrition, metabolic, infection
Bulging/prolapse of nucleus pulposus through a weakened annulus is most common in which direction?
Posterior/posterolateral
- with the outer layers of the annulus still intact
What is a disc herniation?
Nucleus pulposus of intervertebral disc spurts out through a tear in the annulus into either spinal canal or foramen.
What is the difference between a disc prolapse, extrusion and sequestration?
Bulging: outer layers of annulus intact
Extrusion: tear in annulus but nucleus pulposus intact
Sequestration: tear in annulus + portions of nucleus breaks free
What are 2 complications of disc bulging/herniation?
1) Posterior → spinal cord (myelopathy)
- cervical myelopathy
- spasticity
- unsteady gait
- clumsiness in hands
2) Postero-laterally → nerves roots (radiculopathy)
- dermatomal neurological deficits (motor or sensory)
What is rheumatoid arthritis?
Systemic chronic inflammatory autoimmune disease affecting many tissues but principally attacking the joints
Rheumatoid arthritis EPC:
Most common in (M/F)
Age: _____________
Rheumatoid arthritis EPC:
Most common in F
Age: 40-60y
Which part of the body is most common affected by RA, and where are the typical extra-articular areas of involvement?
Articular:
1) PIP and MCP of hand
2) Wrist
3) Elbows
4) Knees
Extra-articular:
1) Skin
2) Heart
3) Blood vessels
4) Muscles
5) Lungs
What are 2 key autoAbs used in the diagnosis of RA?
1) Rheumatoid factor (RF)
2) Anti-citrullinated protein Ab (ACPA)
What is the main genetic predisposition for RA?
HLA-DR4 (MHC Class 2)
Describe the pathogenesis of RA.
Cytokine-mediated CD4+ T cell inflammation
1) Susceptibility
a) genes (eg. HLA) → loss of self-tolerance and lymphocyte regulation
b) environmental (eg. infection, smoking) → enzymatic modification of self proteins
2) CD4+ T cell activation
a) Th1 → M1 macrophage
b) Th17 → cytokines
3) Cell responses:
a) B cell → RF → immune complex deposition → joint injury
b) Cytokines + M1 → joint cell proliferation + enzymes and PGE2
c) Endothelial activation → expression of adhesion molecules → accumulation of inflammatory cells
4) Pannus formation
- destruction of bones, cartilage, fibrosis, ankylosis
What are the 4 pathological features of RA?
1) Synovial inflammation
- chronic inflammatory infiltrate, lymphoid aggregates, exudate, fibrin → swelling and villous formation of the synovium
2) Pannus formation
- granulation tissue → fibrosis → ankylosis
3) Destruction of adjacent bone → joint deformity
4) Formation of rheumatoid nodules
What is the characteristic histological feature of systemic rheumatoid arthritis?
Rheumatoid nodules
- granuloma w central zone of fibrinoid necrosis
- found in many organs
What are 3 systemic effects of rheumatoid arthritis?
1) Rheumatoid nodules
2) Necrotising vasculitis
3) Amyloidosis
What are 2 causes of autoimmune arthritis?
1) SLE
2) Rheumatic fever
3) Systemic sclerosis
What are 4 characteristics of seronegative spondyloarthropathies?
1) Sero-negative (lack of rheumatoid factor)
2) High incidence of HLA B27 Ag
3) Axial location (eg. vertebral/sacro-iliac joint) or asymmetric involvement of peripheral joints in the digits
4) Pathology often in ligamentous attachments rather than synovium
What are 3 forms of seronegative spondyloarthropathies?
1) Ankylosing spondylitis
2) Psoriatic arthropathy
3) Reactive arthrtitis
Where does ankylosing spondylitis usually occur?
Destruction and fibrotic fusion (ankylosis) of vertebral column and sacroiliac joints
Where does psoriatic arthropathy usually occur?
Distal interphalangeal joint
Where does reactive arthritis usually occur?
1) Conjuctivitis
2) Polyarthritis
3) Urethritis
True or false: Disc degeneration is a complex disorder with often multi-factorial etiologies.
True
What is septic arthritis?
Suppurative inflammation of the synovium and joint structures due to infection
How does septic arthritis usually present?
1) Acute onset joint pain
2) Warm, swollen joint
3) Fever
4) Other systemic symptoms
True or false: Septic arthritis is an unconcerning diagnosis as it is usually self-resolving.
False.
Serious condition as it can cause rapid, permanent joint destruction
What are 3 sources of infection in septic arthritis?
1) Hematogenous spread
2) Direct inoculation through skin
3) Contiguous infective spread from adjacent soft tissue abscess or osteomyelitis
What are 4 typical infective agents for septic arthritis?
Bacterial
1) Staph aureus
2) Streptococci
3) Pseudomonas
4) Gram negative bacilli
What is crystal arthropathy?
Deposition of crystal in joints and soft tissues causing arthritis
What are the 2 main forms of crystal arthropathy?
Gout and pseudogout
How do crystal arthropathies usually present?
Acute pain, swelling and redness in joints especially foot and big toe
True or false: Crystal arthropathy can always be distinguished from septic arthritis on physical examination and history.
False. They may be clinically indistinguishable and require joint fluid analysis (gram-stain, culture, crystal analysis)
Gout is characterised by ____________________.
↑serum uric acid and urate crystal deposition
What is the difference between primary and secondary gout?
1°:
- idiopathic
- a/w obesity, alcohol, HTN, fatty diet
2°:
- Due to known conditions that cause hyperuricemia
- eg. drugs, renal failure, familial juvenile nephropathy & congenital enzyme defects
True or false:
All dietary sources of purine should be taken in moderation to reduce the risk of gout?
False.
Plant sources of purines/protein do not increase gout risk
What are 5 risk factors for gout?
1) Male
2) Postmenopausal women
3) Post-transplant patient
4) Alcohol intake
5) High BMI
6) Diet high in meat and seafoods
7) Drugs (eg. diuretics, aspirin, cyclosporine)
Describe the pathogenesis of gout.
1) Excess uric acid → urate crystals
2) Macrophages phagocytose urate crystals → activate inflammatory mediators that release IL-1
3) IL-1 recruit neutrophils → more cytokines, ROS, proteases
4) Neutrophils + Macrophages phagocytose crystals → damage the membranes of lysosomes → release of enzymes
What are 3 ways that hyperuricemia may occur?
1) Overproduction of purines
- eg. high purine diet (meat), de novo synthesis, rare enzymatic defects
2) ↑catabolism of nucleic acids due to high cell turnover (eg. infection, cancer)
3) Decrease uric acid excretion by kidneys
What are 4 acute triggers of gout?
1) Infection
2) Heart attack
3) Alcoholic binge
4) Exercise
What are the long term complications of gout?
1) Deformities
2) Erosions of the joints
3) Gouty tophi
4) Interstitial nephritis
5) Nephrolithiasis
6) Renal failure
What is the appearance of synovial fluid of a gout-affected joint under polarised microscopy?
Strongly birefringent needle shaped crystals
What is pseudogout?
Chondrocalcinosis
- deposition of calcium pyrophosphate dihydrate
What is the pathogenesis of pseudogout?
Alterations in levels/availability of pyrophosphate, phosphate or calcium → crystal shedding
→ ↑ATP breakdown → ↑extracellular PPi → → ↑CPPD in cartilage
What is the cause of pseudogout?
Idiopathic
- a/w trauma, hyperparathyroidism, haemochromatosis
How does pseudogout typically present?
Frequently asymptomatic
- may present as acute/subacute/chronic arthritis
- DDx: OA and RA
What is the appearance of synovial fluid of a pseudogout-affected joint under polarised microscopy?
Rhomboid shaped and positively birefringent crystals
What is crown dens syndrome?
Crowned dens syndrome (CDS) is a clinical and radiological entity consisting of acute neck pain, accompanied by specific radiographic findings of calcifications from calcium pyrophosphate dihydrate crystals superior to and surrounding the dens of the axis, resulting in a “crown-like” appearance on coronal views.
Which parts of bone are commonly affected by osteomyelitis?
1) Cortex
2) Medulla
3) Periosteum
What is the main causative agent of osteomyelitis?
Staph aureus (~90% in all age grps)
- E. coli, GBS in neonates, H. influenzae
- Salmonella in Sickle cell disease
- mixed infection w anaerobes in trauma
- mycobacterial tuberculosis
How does osteomyelitits usually present?
1) Suppurative (acute/chronic OM)
2) Non-suppurative chronic OM/tuberculous OM
3) Pain
4) Fever
5) Swelling
6) Constitutional symptoms
True or false: Upon negative culture of joint aspiration, a suspected case of osteomyelitis should be treated conservatively.
False.
Up to 50% of cases may not grow bacteria on culture, therefore treat aggressively and empirically
What are 3 ways infective agents may enter bone in osteomyelitis?
1) Direct implantation
- eg. trauma w open fracture, wound, surgery
2) Bloodborne spread (eg. lung TB to bone)
3) Extension from contiguous site (eg. middle ear infection → mastoiditis, infection of adjacent soft tissue)
How is osteomyelitis classified?
Suppurative (pyogenic)
Non-suppurative (mainly chronic, fibrotic)
Where does osteomyelitis usually affect children?
1) Long bones (trauma)
2) Jaw (poor dental health)
Where does osteomyelitis usually affect adults?
1) Small bones of foot
2) Femur
3) Vertebral spine
What other joint issue can arise from suppurative osteomyelitis?
Septic arthritis
Describe the progression of osteomyelitis.
1) Suppurative injury
2) Elevation of periosteum
- abscess in subperiosteal space lifts periosteum → impair blood supply → further bone necrosis (sequestrum)
3) Rupture of periosteum
- inflammation of surrounding skin and tissue (cellulitis)
What are 6 sequelae of osteomyelitis?
Healed OM:
1) Resolution (no or minimal scarring)
2) Healing w fibrosis
Complications:
3) Pathological fracture w deformities
4) Spread
5) Progression
6) Bone abscess (Brodie’s abscess)
7) Necrosis of bone (sequestrum)
8) Proliferative periostitis and involucrum
9) Sinus (skin and soft tissue)
10) Secondary amyloidosis
11) Rarely, malignant transformation (bone → osteosarcoma, skin → SCC)
What is Garre’s osteomyelitis?
Garre’s sclerosing osteomyelitis:
- chronic osteomyelitis w proliferative periostitis
- mainly affects childrens and adolescents
- typically involves the jaw → new bone formation obscures underlying native bone structure
- a/w mild irritation, dental infection, trauma
What is a common differential for Garre’s osteomyelitis?
Malignancies (esp clinically and radiologically)
- eg. osteosarcoma, chondrosarcoma
What are 4 possible complications of chronic osteomyelitis?
1) Pathological fracture and deformity
2) Secondary amyloidosis
3) Sepsis or distant spread
4) Malignant transformation
What are the risk populations for tuberculous osteomyelitis?
1) Very young
2) Old
3) Immunosuprressed
4) Developing nations
5) Lower socioeconomic groups
What are 3 complications of tuberculous osteomyelitis in the vertebral spine?
(Most common in thoracic and lumbar)
1) Compression fracture
2) Severe deformities (scoliosis, kyphosis)
3) Neurological deficits due to cord and nerve compression
