Pathology Flashcards
1
Q
Name the types of arthritis
A
- osteoarthritis
- rheumatoid arthritis
- seronegative spondyloarthopathies
- infectious arthritis
- crystal induce arthritis
2
Q
Describe connective tissue diseases
A
- autoimmune conditions
- inflammatory diseases characterised by the presence of autoantibodies
- 1-2% of the population
- often present with MSK and rheumatological symptoms and signs but have potential for systemic manifestations
3
Q
Describe synovial joints
A
- have a joint space that allows movement
- strength from capsule, ligaments and muscle
- joint space is bounded by synovial membrane; produce synovial fluid for lubrication and nutrition
- articular surfaces formed of hyaline cartilage; elastic shock absorber and wear resistant surface
- disseminate shear forces effectively
- type 2 collagen gives strength
- water and proteoglycans give elasticity and reduce friction
4
Q
Describe osteoarthritis
A
- the most common form of joint disease; an important cause for joint replacement surgery
- a degenerative form of joint disease; degenerative changes in the articular cartilage, structural changes and functional impairment
- pathogenesis; aging and biomechanical stress
5
Q
What is primary osteoarthritis?
A
- insidious
- no overt cause
- age related
6
Q
What is secondary osteoarthritis?
A
- predisposing condition
- excess / inappropriate weight bearing, deformity, injury, systemic conditions
7
Q
Describe the clinical correlations of osteoarthritis
A
- insidious onset
- primary form present from age >50
- secondary forms may arise earlier
- aches and pain; worse with use
- usually hips, knees, lower lumbar and cervical vertebrae, PIP and DIP joints of fingers
- wrists, elbows and shoulders usually spared
8
Q
Describe the early events of pathogenesis in osteoarthritis
A
- degeneration of the cartilage and disordered repair
- injury to chondrocytes and matrix
- chondrocyte injury; genetic and biochemical factors
- chondrocytes proliferate; release inflammatory mediator, proteases, collagen and proteoglycans, remodelling and degeneration of cartilage
9
Q
Describe the late events of pathogenesis in osteoarthritis
A
- stimulate inflammatory changes in synovium and subchondral bone
- repetitive injury and chronic inflammation
- loss of chondrocytes
- disruption to and loss of cartilage matrix
- further changes in subchondral bone and synovium
10
Q
Describe the early pathological features of osteoarthritis
A
- damage to cartilage
- clusters of chondrocytes
- small fissures in cartilage
- fibrillation
11
Q
Describe the later pathological features of osteoarthritis
A
- cartilage is completely worn away; bone on bone
- subchondral cysts
- surface becomes polished - eburnation
- remodelling to cope with stress
- formation of osteophytes
12
Q
Describe eburnation
A
- loss of articular cartilage
- joint space being formed by the bone that normally lies underneath the cartilage becomes smooth through trauma
13
Q
Osteophytes can do what?
A
They can innervate nerves
14
Q
Describe rheumatoid arthritis
A
- a chronic inflammatory disorder
- autoimmune
- 2nd to 4th decades
- 3F:1M
- often presents with features of arthritis
- a systemic disorder
- extra-articular lesions are common; may occur in the absence of joint symptoms
15
Q
Describe the presentation of rheumatoid arthritis
A
- vague systemic features; malaise, fever
- generalised musculo-skeletal pain
- joint involvement become more apparent
- symmetrical; swollen, warm, painful, limited movement in morning and after inactivity
- small joints before large joints; hands and feet (MCP, MTP, PIP), wrists, ankles, elbows, knees, cervical spine, usually spares hips and lumbosacral joints
16
Q
Describe the progression of symptoms in rheumatoid arthritis
A
- joint swelling, decreased range of movement, joint fusion (ankylosis)
- associated involvement of tendons ligaments; joint deformity
- unstable (very) limited ROM
- synovial herniation; cysts eg bakers cyst
- joint effusions, peri-articular bone loss, loss of articular cartilage
- disease can show periods of remission
- 10% patients have acute presentation; severe symptoms and polyarticular disease
17
Q
Describe the genetic factors of rheumatoid arthritis
A
- HLA DRB1 alleles linked to RA have common structure in the beta chain (shared eptiope), a site for binding arthritogens
- initiate autoimmune inflammatory reaction
- immune tolerance compromised
18
Q
Describe environmental factors of rheumatoid arthritis
A
- environmental factors
- precise trigger uncertain
- infection and smoking increase citrullinated peptide
- citrullination of self proteins
- modify epitopes and trigger autoimmune reactions
19
Q
Describe the immunology of rheumatoid arthritis
A
- auto-immune inflammation triggered
- CD4+T cells may be critical
- cytokine production results from initiation of inflammation
- IFNg activates macrophages and synovial cells
- IL-17 recruits neutrophils and monocytes
- TNF and IL-1 stimulate production of proteases from synovium
- RANKL expressed on activated T cells stimulates bone resorption
20
Q
What is involved in the acute phases of rheumatoid arthritis?
A
- pannus formation; inflammatory granulation tissue
- hyperplastic / reactive synovium
- cartilage is destroyed by inflammatory process; loss of joint space
21
Q
Describe the extra-articular disease involved with rheumatoid arthritis
A
- 40% of cases
- before, with or after joint symptoms become apparent
- high titres of RF most at risk
- tendons, ligaments and fascia
- many other sites of involvement
22
Q
What are rheumatoid nodules?
A
Areas of necrotic cartilaginous tissue surrounded by a periphery of inflammatory cells
23
Q
Describe the skin manifestations of rheumatoid arthritis
A
- rheumatoid nodules; 25% of patients, often severe disease, pressure points, internal organs eg lung, spleen, heart
- necrotising granuloma
- small vessel vasculitis; splinter haemorrhages, peri-ungal infarcts, ulcers, gangrene
- associated with episcleritis, pleural and pericardial effusions
- pyoderma gangrenosum
24
Q
What are necrotising granulomas?
A
- central area collagen necrosis
- surround palisade of macrophages (lymphocytes and plasma cells)
25
What are the ocular manifestations of rheumatoid?
- keratoconjunctivitis
| - episcleritis and scleritis
26
What are the oral manifestations of rheumatoid?
- salivary gland swelling
| - sjogrens syndrome
27
What are the GI manifestations of rheumatoid?
- mesenteric vasculitis (rare)
| - related to medication
28
What are the pulmonary manifestations of rheumatoid?
- pleuritis and effusion
- rheumatoid nodules
- interstitial lung disease; interstitial fibrosis
29
What are the cardiac manifestations of rheumatoid?
- pericarditis and effusion
- myocarditis; conduction anomalies
- endocarditis; valve dysfunction
30
What are renal manifestations of rheumatoid?
- forms of glomerulonephritis
| - amyloid disease; nephrotic syndrome
31
What are neurological manifestations of rheumatoid?
- peripheral neuropathy
| - cervical myelopathy; atlanto-axial disease
32
What are haematological manifestations of rheumatoid?
- anaemia; chronic disease, iron deficiency
- other abnormal indices
- lymphadenopathy; hyperplasia
- splenomegaly (feltys syndrome)
- increased risk of lymphoma
33
What are seronegative spondyloarthopathies ?
- group of diseases with some common features
- HLA B27 association
- No rheumatoid factor
- involve sacro-iliac joints +/- others
- affect ligamentous attachments
34
Describe psoriatic arthritis
- >10% of patients with psoriasis
- predominantly affects joints of hands and feet
- 20% of cases involve sacro-iliac joints
- joint involvement may be asymmetrical
- DIP joints characteristically affected
- similar histology to RA
35
Describe infectious arthritis
- potentially destructive process
- suppurative
- haematogenous spread of organisms; s aureus in adults, gonococcal infection in young adults, sickle cell predisposes to salmonella arthritis
- typically involves single joint (knee most common)
- systemic features of infection
- acutely painful and swollen joint; aspirate purulent fluid
- mycobacterial, lyme disease, viral
36
Describe hyperurucaemia
- can be a problem with excess synthesis or problem with excretion
37
Describe synthesis of uric acid
- from purine catabolism
- reflects abnormal purine metabolism
- synthesis from non-purine precursors
- salvage from dietary intake and catabolism of purine nucleotides
38
Describe excretion of uric acid
- renal filtration
- reabsorbed in proximal tubule
- limited excretion from distal tubule
39
Describe the increased production of uric acid
- usually idiopathic; unknown enzyme defect
- known enzyme defect; HGPRT deficiency; lesch nyhan syndrome (rare), impairs purine nucleotide salvage pathway, degraded to urate
- increased cell turnover; psoriasis, cancer and tumour lysis following chemotherapy
40
Describe the reduced excretion of uric acid
- under excretion; a common cause of gout, chronic renal disease
- drug side effect; thiazide diuretics reduce urate excretion
41
Deposition of crystals into soft tissues causes what
| ?
Gouty tophus
42
Describe the cytology findings in gout
- joint fluid examined under cross polarised light to detect needle shaped crystals
43
Describe the histology of gout (tophus)
- amorphous eosinophilic debris and inflammation (giant cells)
- crystals lost during tissue processing
- NB; pyrophosphate arthropathy
44
Describe calcium pyrophosphate
- common crystal arthropathy; pseudogout or chondrocalcinosis
- usually older invidiuals - large joints
- may be known cause - hypercalcaemia, haemochromatosis, hypomagnesaemia, ochronsis, hypothyroidism
- usually idiopathic
- dense deposits on xray
45
Describe pseudogout
- usually asymptomatic
- incidental finding on xray
- also range of joint pain; acute chronic etc
- crystals aren't distinct histologically
- under polarised light; rhomboid shaped crystals, weak positive birefringence, thicker and bigger than needle shaped urate crytsals
- crystals form in cartilage, menisci and discs
46
Name some examples of non-neoplastic bone disease
- osteoperosis
- osteomalacia
- hyperparathyroidism
- avascular necrosis
- pagets
47
Describe osteoperosis
- decreased bone mass
- osteoperosis >2.5 SD below mean peak bone mass
- associated with significant risk of fracture; atraumatic or vertebral compression fracture
- localised; disuse
- generalised; primary and secondary
- generalised most associated with osteoperosis
48
Describe causes of secondary osteoperosis
- endocrine disorders; cushing, hyperparathyroidism, hyperthyroidism
- GI disorders; hepatic insufficiency, malabsorption, malnutrition, deficiency of vit C and D
- drugs; alcohol, corticosteroids
- immobilisation
49
Describe age related changes and osteoperosis
- reduced proliferative and biosynthetic capacity of osteoblasts
- response to growth factors attenuated
50
Describe reduced physical activity and osteoperosis
- disuse, elderly and astronauts vs athletes
| - load magnitude more effective than endurance
51
Describe genetic factors and osteoperosis
- polymorphisms in genes regulating osteoclastic activity and vitamin D receptors
52
Describe calcium and osteoperosis
-Ca deficiency, elevated PTH and low vitamin D
53
Describe hormonal effects and osteoperosis
- post menopausal
- low oestrogen causes high bone turnover but osteoclasis exceeds osteoblastic activity
- monocytes release inflammatory mediators
54
Deficiency of vitamin D leads to what?
- hypocalcaemia and PTH elevated
- increase calcium absorption
- increased osteoclastic activity and release of Ca from bone
- reduce renal calcium loss
- increase renal excretion of phosphate; low phosphate impairs bone mineralisation
55
Describe osteomalacia
- impaired mineralisation of bone matrix
- bone remodelling occurs normally
- newly formed osteoid is not fully mineralised; thick osteoid seams
- bone is weakened - prone to fracture; micro-fractures, gross fractures
56
Describe avascular necrosis (AVN)
- necrosis of bone and marrow; can be asymptomatic, resultant bone and joint damage can lead to THR
- the result of loss of effective vascular supply; can result from fractures (scaphoid, femoral head)
57
Name predisposing conditions of AVN
- alcohol
- corticosteroids, biphosphonates
- connective tissue disorders
- decompression (the bends)
- sickle cell disease
- infection, pregnancy, pancreatitis, radiation
58
Describe PTH
- activated osteoclasts; increased bone resorption, releases calcium
- increased resorption of calcium by renal tubules
- increased urinary phosphate excretion
- increased synthesis of active forms of vitamin D
59
Describe parathyroidism
- elevates serum calcium, normally inhibits PTH release
- continued osteoclasis; decreased bone mass, deformity and degenerative joint disease
- osteoperosis, brown tumours and osteritis fibrosa cystica
60
Describe osteoporosis
- generalised
- phalanges, vertebrae and femur
- prominent changes in cortical bone; medullary cancellous bone also affected, dissecting osteitis
- fibrovascular tissue in marrow spaces
61
Describe brown tumours and hyperparathyroidism
- osteoporotic bone prone to fracture
- associated haemorrhage elicits macrophage reaction and processes of organisation and repair
- includes giant cells
- mass of reactive tissue known as a brown tumour
- can become cystic
62
Describe pagets disease
- abnormality of bone turnover
- osteitis deformans
- late adulthood
- geographic variation in incidence
- often asymptomatic
- cause uncertain
- genetic elements
63
Describe the three stages of pagets disease
- osteolytic; resorption pits with large osteoclasts
- mixed; osteoclasis and osteoblastic activity
- osteosclerotic
64
What is the net result of pagets disease?
- thick excess bone with abnormal reversal lines; mosaic pattern
- bone matures but is soft and porous
65
Name some causes of pathological fracture
- many causes
- osteoporosis is very common
- tumours
- benign; usually children and primary
- malignant; adults and metastatic
66
What causes avascular necrosis?
- usually asymptomatic
- trauma (scaphoid), alcohol, dysbarism, steroid injection, sickle cell disease, infection etc
- alcohol; unclear mechanism, atherosclerosis related?
67
Describe the practical issue with biopsy procedure
- the more tissue the better
- may need extensive examination
- suspected malignancy can require numerous stains
- ancillary investigation eg genetic studies may be crucial
68
Name examples of soft tissue tumours
- ganglion cyst, rheumatoid nodules, gouty tophus, tenosynovitis
- proliferative conditions; nodular fasciitis, fibromatoses
- benign tumours; lipoma, haemangioma, neurofibroma, schwannomas, leiomyoma
- malignant tumours
69
What are the karyotypic abnormalities of synovial sarcoma?
t(X;18)
70
What is the karyotypic abnormalities of alveolar rhabdomyosarcoma?
t(2;13)
71
What is the karyotypic abnormality of ewings sarcoma?
t(11;22)
72
Name some common and benign lesions
- ganglion cyst
- giant cell tumour
- fibromatosis
- rarer; fibrous cortical defect
- fibrous dysplasia
73
Describe ganglion cysts
- lump near a joint capsule or tendon sheath
- commonly arise around the wrist
- degenerative change within connective tissue
- not a true cyst; no epithelial lining
- histologically; space with myxoid material
- secondary inflammatory changes
- synovial cysts can result from herniation of synovium or bursal enlargement eg bakers cysts
74
Describe nodular fasciitis
- superficial or deep
- usually less than 5cm
- circumscribed usually
- very cellular, lots of mitoses
- plump cells; stellate and spindle
- tissue culture appearance
- haemorrhage
- mature towards periphery
- correlates with site and history
- spontaneous resolution; do not recur
75
Describe myositis ossificans
- similar to nodular fasciitis
- history of preceding trauma
- associated with insertions of large muscles of arms and legs
- cellular proliferation but with evidence of bone formation and, critically, zonation
- recognition of organisation is critical
- may also be evident radiologically
- but in early stages can e difficult and suggest malignancy
76
Describe dupuytrens
- common superficial fibromatoses
- knuckle pads, plantar
- penile - peyronies
- M>F
- average age 60
- idiopathic
- recognised associations; alcohol, DM and anticonvulsants
77
Describe deep fibromatosis
- desmoid tumour
- large infiltrative masses
- do not metastasise
- often young adults (teenage to 30s)
- sites; musculo-aponeurotic tissue of abdominal wall, mesenteric tissue, limb girdles
- mutations of APC or b catenin genes; gardners syndrome predisposed to develop deep fibromatoses
78
Describe tenosynovitis
- giant cell tumour of tendon sheath
- digits and wrist
- reactive proliferation
- excise and rarely recur
- pigmented villonodular synovitis
- similar histology
- large joints
- more likely to recur
79
Describe angiolipomas
- usually multiple and peripheral
- vascular with fibrin thrombi
- one of the painful subcutaneous lesions
80
Describe liposarcoma
- one of the most common sarcomas
- adults, 50 to 60s
- deep soft tissue of extremities or retroperitoneum
- histological subtypes; well differentiated, myxoid, pleomorphic, amplification
81
Grading of sarcomas relied on what three features?
- degree of differentiation
- degree of proliferation; mitotic count
- presence of coagulative necrosis
82
Describe leiomyosarcomas
- 10-20% soft tissue sarcomas
- F>M
- deep soft tissues of the extremities and retroperitoneum
- can arise from great vessels eg IVC
- size, location and grade affect treatment options and prognosis
- if excision not complete recur and can be lethal due to local invasion and metastasis - haematogenous to lungs
83
Describe leiomyomas
- leiomyomas are one of the most common tumours in the body; uterine
- rarely encountered in orthopaedic practice
84
Describe rhabdomyosarcoma
- aggressive tumours
- surgery plus adjuvant therapy
- embryonal subtype arising in walls of hollow structures (botryoid variant) has best prognosis
- pleomorphic forms may be hard to identify without ancillary investigations
