pathology Flashcards
what are the main types of arthritis
osteoarthritis
rheumatoid arthritis
psoriatic arthritis
fibromyalgia
gout / pseudo-gout (crystal arthropathy)
osteoarthritis
degenerative changes in articular joints
aging and biochemical stress:
>primary - insidious, no overt cause, age related
>secondary - predisposing cause, excess inappropriate weight bearing/deformity/injury/systemic conditions
an important cause for joint replacement surgery
when do primary forms of OA present
> 50yrs
when do secondary forms of OA present
earlier in life
pathogenesis of OA
degeneration of cartilage and disordered repair
injury to chondrocytes leading to remodelling of bone, due to active chondrocyte response in the articular cartilage and the inflammatory cells in surrounding tissues
> chondrocyte inflammation > can only get worse > stimulate changes in synovial and subchondral bone
repetitive injury
early changes of OA
damage to cartilage
clusters of chondrocytes
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eburnation
loss of articulate cartilage
/ subchondral sclerosis
later changes
osteophyte
projection of the cartilage
/ disorganised bone remodelling
> can irritate nerves
subchondral cysts
accumulation of cartilage fluid
RA
autoimmune, symmetrical
chronic inflammatory disorder
presents more in women 3f:1m
relatively young people can get it ie presents commonly in 2nd and 4th generations
presents with features of arthritis:
occurs in - synovium, peripheral joints, PIPs, MCPs, and can take systemic effects
a systemic disorder
extra-articular disease can be seen:
rheumatoid nodules over pressure points/ can be seen over internal organs as well
RA symptoms
symmetrical
malaise, fever
generalised MSK apin
joint involvement becomes apparent :
-symmetrical : swollen warm painful joints
worse in the morning and get better with movement
RA progression
> joint swelling, decreased range of movement, joint fusion (ankylosis)
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RA - genetic factors
HLA DRB1
HLA DR4
RA - environmental factors
infection and smoking
citrillunation of proteins ie collagen, filaggrin and fibronectin
RA - immunology mechanism of action ie what cytokines etc
IFNG
IL-17
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acute phase of RA
pannus formation - hyperplastic and reactive synovium
cartilage is destroyed - loss of joint space
chronic phase of RA
what is the rheumatoid nodule
essential area is necrotic tissue and surrounding that are histiocytic cells (darker) ie granulation
it is a necrotising granuloma
what are the other extra articular manifestations of RA
there’s just too many
Resp:
pneumonitis - from methotrexate use
pul. fibrosis
pleural effusions
CV:
raynauds
valvulitis
endocarditis
pericarditis
LVF
renal:
glomerulonephritis
eyes:
scleritis
dry eyes
anterior uveitis
mucocutaneous:
alopecia
oral/nasal ulceration
malar rash
photosensitivity
systemic sclerosis
seronegative sponfyloarthritides features
HLA B27
ie ankylosing spondylitis , reactive and enteritis associated arthritis
ankylosing spondylitis
presents in 2nd to 3rd generations of life
males more affected
mainly affects:
sacro-iliac joints / spine
psoriac arthritis
predominantly affects joints of hands and feet
> 10% of patients have psoriasis
infectious arthritis
potentially destructive
suppurative - haematogenous spread of organisms
involves a single joint - usually a knee joint
acutely painful and swollen joint - would aspirant purulent fluid
ie mycobacterial ,Lyme, viral, Staph A
crystal arthropathy
gout - deposition of urate crystals
-hyperuriceamia is necessary but not sufficient
pseudo gout - calcium pyrophosphate
>common
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MoA of hyperuriceamia
synthesis from purine catabolism
excretion via renal
why for synthesis ?
-usually idiopathic
-HGPRT deficiency (enzyme) Lesch Nyhan syndrome
-increased cell turnover ie cancer , psoriasis
why for excretion ?
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MoA of hyperuriceamia
synthesis from purine catabolism
excretion via renal
why for synthesis ?
-usually idiopathic
-HGPRT deficiency (enzyme) Lesch Nyhan syndrome
-increased cell turnover ie cancer , psoriasis
why for excretion ?
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how do crystals end up in the joints ?
unclear -
trauma
happens in joints with lower temperatures
precipitation of crystals - alcohol /drugs /obesity
clinical manifestation of crystals arthritis
secondary degenerative changes
deposition in soft tissues - gouty trophy
renal disease - stones and direct deposition in tubules and interstitium
pathological findings of gout / hypercalceamic arthropathy
cytology = needle shaped crystals
histology (typhous) = amorphous eosinophilic
pseudo gout clinical findings
usually asymptomatic
incidental finding on X-ray
range in joint pain
rhomboidal crystals and not as strongly ‘fluorescent”
what is the most common arthritis
OA
pathogenesis of citrullinated proteins in RA
what is osteoporosis
-decreased bone mass
-associated with significant risk of fracture
-can be localised or generalised
localised osteoporosis cause
disuse
generalised osteoporosis cause
primary = idiopathic , post-menopausal , senile
secondary =
endocrine - cushings
GI disorders,
drugs,
misc.
when do we have peak bone mass
young adulthood
factors affecting = hereditary, diet, physical activity, muscle strength, hormonal
factors for osteoporosis
genetic
age related changes
reduced physical activity
hormonal effects
calcium
what is osteomalacia
concerned with vit D deficiency - via sun, diet
impaired mineralisation of bone matrix - newly formed osteoid seams, thick
> the bone is weakened and prone to fracture
vitamin D function
stimulates absorption of calcium
osteoblasts stimulated to release osteocalcin
what is avascular necrosis (AVN)
necrosis of bone and marrow
the result of loss of effective vascular supply - can result from fractures
predisposing conditions for avascular necrosis
alcohol
corticosteroids
connective tissue disorders
decompression (the bends)
sickle cell disease
infection, pregnancy
what would AVN in the femoral head look like
wedge shape infarct and is often subchondral
-essentially looks like another border
what is creeping substitution
when new bones grows over dead bone
hyperparathyroidism - how does it come about
elevated calcium signals to stop PTH release but not in HPPT
normal function and MoA of PTH
-
what happens to bones in HPPT
cont. osteoclasis
osteoporosis
brown tumours - osteitis fibrosa cystic
what is a brown tumour
> osteitis is late stage
what is renal osteodystrophy
Paget’s disease
abnormality of bone turnover
occurs in late adulthood
often asymptomatic
osteitis deformas
Paget’s disease causes
uncertain
genetic = SQSTM1/p62
RANKL
viral infection ie measles
the three stages of Pagets
osteolytic - reabsorption pits with large osteoclasts
mixed - osteoclasis and osteoblastic activity
osteosclerotic
net result = mosaic pattern = thick excess bone with abnormal reversal lines
what bones are most commonly affected in Pagets and what happens
usually axial, small bones are less affected
enlargement and abnormal shape , platybasia , sabre tibia
increased metabolism - high level of alkaline phosphatase
increase of malignancy - osteosarcoma
