PATHOLOGY Flashcards
what is rickets
defective mineralization of growth plates in children (open growth plates )
what does rickets result in
- reduced apoptosis of hypertonic chondrocytes in the growth plate
- reduced mineralization of primary spongiosa in the metaphysis
what are symptoms of rickets
- bone pain
- growth retardation
- delayed achievement of motor milestones
- bony deformities e.g. bowlegs
- muscle weakness due to hypocalcemia or hypophosphataemia
what is osteomalacia
defective mineralization of existing bone during remodeling process
what happens in osteomalacia
bone softening
occurs everywhere in bones of adults (closed growth plates)
what are symptoms of osteomalacia
- proximal muscle weakening and wasting
- myalgias and arthralgias
- muscle spasms
- altered or waddling gait
- spinal,limb or pelvic deformities
what causes rickets and osteomalacia
low dietary ca2+ or inability to absorb it
low vitamin D
what are sources of vitamin D
- made in human skin (D3) after exposure to UV light
- ingested in food (D2) found in plants and D3 in animal products
which organs convert vitamin D and to what
liver to calcidiol (25-hydroxyvitamin D)
kidney to calcitriol (active hormone 1,25 dihydroxyvitamin D)
what is the function of calcitriol in low ca2+ conditions
- increased absorption of dietary calcium
- increased reabsorption of calcium from kidney
- releasing calcium from bone store
how is ca2+ absorbed from the diet
- in the jejunum
- when the conc is low active transport takes place
how is ca2+ reabsorbed in the kidney
-distal tubular calcium re-absorption involves a transcellular mechanism
how is ca2+ conc increased by bone resorption
- at low ca2+ levels the bone is broken down
- calcitriol appears to increase expression of RANKL in osteoblasts resulting in increased osteoclast formation
what are the risk groups of rickets and osteomalacia
- significant poverty
- low food availability
- diets low in calcium
- seasonal lack of sunlight
- older age reduced bone formation and less ca absorption from diet
what is rheumatoid arthritis
a chronic autoimmune disease that causes inflammation of affected joints resulting in cartilage destruction and bone erosion
what are the early signs of rheumatoid arthritis
- fatigue
- flu like feeling
- swollen tender joints
- morning stiffness
what are the more advanced symptoms of rheumatoid arthritis
- pleural effusions
- lung nodules and interstitial lung disease
- lymphomas
- atheroscelrosis
- joint malalignment
- loss of range of motion
what are the clinical manifestations of RA
- octular
- pulmonary
- skin
- gastrointestinal
- neurological
- vascular
- cardiac
- renal
- muscular skeletal
- haematological
what causes RA
- genetic predisposition of the respective patient resulting in generation of auto reactive T and B cells
- a triggering event e.g. a viral or bacterial infection
what is autoimmune tissue destruction presented as
synovitis which is inflammation of the joint capsule i.e. synovial membrane and synovial fluid
what is the joint inflammation maintained by
- dendritic cells
- T cells
- macrophages
- neutrophils
- fibroblasts
- osteoclasts
what does the chronic inflammation lead to
expansion of the synovial membrane which invades the periarticular bone at the cartilage bone junction and this results in bone erosion and cartilage degradation
which cells start the process of RA
auto reactive Th1 or Th17 primed in the lymph nodes
what do the activated auto reactive T cells do
activate the macrophages and fibroblasts
what do activated macrophages do
secrete large quantities of strongly pro inflammatory cytokines and this matins an inflammatory environment in the synovium
what do the activated fibroblasts do
produce RANK-L promote the differentiation of osteoclasts from macrophages and leads to cartilage destruction and erosion
what are the treatments for RA
-NSAIDs, immunosuppressive glucocorticoids and disease modifying anti-rheumatic drugs (DMARDs)
