Disorders of MSK I&II - Zaloga Flashcards
1
Q
osteoclasts
A
- resorb bone causing release of Ca2+
- remodeling of skeleton
- macrophages clean up cellular debris
- has RANK receptor to activate NFkB for survival
2
Q
osteoblasts
A
- form new bone
- activate osteoclasts with RANKL and M-CSF
- contain LRP5/6 receptor for WNT binding to activate beta-catenin and OPG…inhibited by sclerostin
- contain RANKL
3
Q
OPG - osteoprotegrin
A
- decoy receptor produced by osteoblasts
- binds to RANKL preventing binding to RANK receptor
4
Q
hereditary bone disorders
A
- Achondroplasia
- Osteogenesis Imperfecta (Type 1 collagen disease)
- osteopetrosis
5
Q
achondroplasia
A
- most common dysplasia
- dwarfism
- FGFR3 mutation (always active) –> inhibiting endochondral growth –> no ossification in appendicular skeleton
- short extremities
6
Q
osteogenesis imperfecta (type 1 collagen disease) aka brittle bone
A
- most common connective tissue disorder
- affect type 1 collagen –> brittle bones, fractures
- blue sclera, hearing loss
7
Q
osteopetrosis aka marble bone disease
A
- brittle, fragile bones –> easy fractures
- mutations of osteoclasts resorption –> reduced resorption –> sclerosis
- adult is benign and infantile is malignant
- decreased hematopoiesis –> anemia
- adult: autosomal dominant –> defect in chloride channel function
- infant: autosomal recessive: proton pump or chloride channel dysfunction
8
Q
bone and cartilage acquired disorders
A
- osteopenia and osteoporosis
- osteomalacia and rickets
- Paget disease
- osteitis fibrosa cystica
9
Q
osteoporosis
A
- severe osteopenia
- primary, idiopathic, senile - low proliferative osteoblasts (low turnover), postmenopausal - low estrogen, cytokines stimulate osteoclasts with high RANKL and low OPG (high turnover)
- normal bone content, low quantity, thin trabeculae
- dexa scan measure density
- high risk fractures
10
Q
rickets and osteomalacia
A
- vit. D deficiency –> under mineralized bone
- rickets (children) –> interferes with growth plates
- osteomalacia (adults) –> undermineralized bone
11
Q
Paget disease aka osteitis deformans
A
- increase bone, but disordered (risk of fractures)
- lamellar bone in sclerotic phase
- high alkaline phosphatase
- mutations in SQSTM1 gene –> increase NFkB –> increase osteoclast activity
phases:
Osteolytic – osteoclasts resorbing bone
Mixed – osteoblasts enter to repair
Sclerotic – dense, weak bone due to osteoclasts breaking it down
12
Q
osteitis fibrosa cystica
A
- loss of bone mass
- calcified structures replaced with fibrous –> weak bones
- cyst like brown tumors
- causes: PTH (increase serum Ca2+ and osteoclasts), renal disease (cannot make vit. D)
- brown tumor –> decrease in bone density/mass
13
Q
fracture repair process
A
- rupture blood vessels –> hematoma fills gap –> fibrin mesh –> influx of inflammatory cells and fibroblasts –> new capillaries
- 1st week –> hematoma and remodel fractured ends of bone
- 2nd week –> soft tissue callus to bony callus - stiffness and strength increase with more mineralization
14
Q
osteonecrosis (avascular necrosis)
A
- dead bone (necrotic) –> few osteocytes
- causes: fractures or corticosteroids
- vascular insufficiency
- subchondral and medullary infarcts
- trabeculae collapsed and not repaired
15
Q
osteomyelitis
A
- inflammation of bone and marrow, sclerosis
- usually due to infection
- dead bone, fibrosis, infiltrate of inflammatory cells
- pyogenic bacteria and mycobacteria (fungal)
- mycobacterial –> tuberculous spondylitis (Pott disease)
- staph 90% cause for pyogenic
- E. coli, pseudomonas, klebsiella in IV drug and GU tract infections
- H. influenza in neonates (not vaccinated)
- sickle cell –> salmonella
- treatment: antibiotics and drainage
- acute neutrophils, chronic lymphocytes
- infection breaks periosteum –> form sinus tract
16
Q
osteoarthritis aka degenerative joint disease
A
- degeneration of cartilage, disordered repair
- previous joint injury and obesity predisposing factors
- NO FUSION of joints
- inflammation –> chondrocyte death –> bone eburnation, thickened trabeculae, subchondral sclerosis
- fracture gaps can form synovial cysts and osteophytes
- osteophytes in Heberden’s and Bouchard’s nodes**
17
Q
rheumatoid arthritis (RA)
A
- chronic inflammation, autoimmune
- attack joints –> synovitis, lose joint space
- cartilage destruction with ankylosis (FUSION)
- osteopenia
- radial deviation of wrist, ulnar deviation of fingers
- self antigens attacked by antibodies and CD4 T cells
- cytokines: IFN-gamma (Macs), IL17 (neutrophils), monocytes
- T cells activate RANKL –> bone resorption w/ osteoclasts
- anti-CCP (citrullinated peptides) for diagnostic marker - autoantibodies
- rheumatoid factor –> IgM, IgA binding Fc on IgG activating immune system
- Pannus destroys cartilage –> fibrous –> bone ankylosis
18
Q
seronegative spondyloarthropies
A
- Ankylosing Spondylitis
- psoriatic arthritis
- reactive arthritis
swelling of fingers/toes, changes in ligament attachments, no rheumatoid factor, HLA-B27, T cell attacks antigen
19
Q
Ankylosing Spondylitis aka rheumatoid spondylitis (Marie-Strumpell)
A
- destroy articular cartilage
- bone ankylosis (sacroiliac joints common)
- 90% HLA-B27 positive
- low back pain, spinal immobility
20
Q
psoriatic arthritis
A
- psoriasis, chronic inflammation
- peripheral and axial joints (ex. hands, feet mainly) - distal joints
- joint destruction not frequent
- HLA-B27 and HLA-Cw6 alleles
21
Q
reactive arthritis aka Reiter’s syndrome
A
- joint pain, swelling due to infection of another part of body
- triad: urethritis or cervicitis, conjunctivitis, and arthritis
- GU tract infection (chlamydia)
- GI tract infection (shigella, salmonella, campylobacter)
- 80% HLA-B27 positive
22
Q
Gout
A
- crystals include monosodium urate (needle like)
- attacks of acute arthritis by crystals in/around joints –> cytokine cascade –> destroy joints
- hyperuricemia, MSU crystals cause inflammation, cytokines recruit Macs (inflammasome) to recognize crystals and cause inflammation
- repeated attacks –> tophaceous gout –> pannus destroys cartilage w/ ankylosis
- cause: hyperuricemia, renal failure, obese, EtOH
- men more affected
23
Q
Pseudogout aka chondrocalcinosis
A
- crystals include Ca2+ pyrophosphate dehydrate, CPPD, (rhomboid shape)
- sexes/races equally affected
- activation of macrophages inflammasome –> inflammation
- more mild than gout
24
Q
peripheral nerves neuropathy
A
- contain axons and myelin sheaths (Schwann cells)
- damage to proteins that make myelin (MBP, MPZ, PMP22, PRX) or Schwanna cells –> disease and slow nerve conduction
- pseudotumor if transected ends not close together for repair
25
Q
axon neuropathy
A
- due to trauma or entrapment (ex. lacerations, fractures)
- morton neuroma - nerve compression due to painful mass in foot, fibrosis
- traumatic neuroma - fibrosis around nerve
26
Q
Gullian Barr syndrome
A
- acute inflammatory demyelinating polyneuropathy
- T cell immune response –> demyelination by Macs and antibodies attacking nerve fibers
- ascending paralysis, areflexia, slow conduction velocity
- begins distally, invades proximally
27
Q
neuromuscular junction
A
- presynaptic depolarization –> Ca2+ channels release ACh vesicles –> bind to receptors on motor end plate (postsynaptic sarcolemma) –> contraction
Diseases: Myasthenia Gravis, Lambert-Eaton myasthenic syndrome
28
Q
myasthenia gravis (Graves)
A
- autoantibodies against ACh receptors
- painless weakness, may affect ventilation
- associated with thymoma and thymic hyperplasia –> treat with thymectomy in some cases
- ptosis and diplopia
- treatment: AChE inhibitors, immunosuppressive to decrease antibodies, thymectomy
29
Q
Lambert-Eaton myasthenic syndrome
A
- antibodies attack presynaptic Ca2+ channel –> prevent ACh release –> weakness of extremeties
- repetitive stimulation –> increase muscle response
- associated with neuroendocrine carcinoma of lungs
30
Q
skeletal muscle atrophy
A
- normal - one nerve innervates same fiber type
- denervation when axons are damaged –> myofiber atrophy
- reinnervation of myofibers –> switch of fiber type and regeneration of fibers –> type grouping
- degeneration –> release creatine kinase
- regeneration –> satellite cells fuse with damaged myofibers
- replaced with fibrosis and fat with chronic disease where regeneration fails
31
Q
inflammatory myopathies
A
- polymyositis
- dermatomyositis
- inclusion body myositis
autoimmune inflammatory disease –> autoantibodies, HLA-DR genotypes
32
Q
Dermatomyositis
A
- autoimmune –> proximal muscle weakness, skin changes
- Anti-Mi2 antibodies –> heliotrope rash, Gottron papules
- Anti-Jo1 antibodies –> interstitial lung disease, mechanic hands, arthritis
- myalgia, high serum creatine kinase
- perifascicular atrophy (inflammatory infiltrate of muscle edges) due to CD4 cells –> associated with blood vessel injury
33
Q
Polymyositis
A
- same as dermatomyositis, but no skin changes
- muscle weakness and myalgia
- CD8 T cells infiltrate instead
- no perifascicular atrophy or vascular injury
34
Q
inherited myopathies
A
- congenital: central core disease, NEM, centronuclear, congenital fiber type disproportion –> floppy infant
- muscular dystrophies –> progressive muscle damage (ex. Duchenne, Becker)
- mutated dystrophin –> X linked
- mutated caveolin and sarcoglycan –> limb-girdle dystrophies
- genetic testing for dystrophin to confirm
- + Gower’s sign –> impaired lower extremeties
- high creatine kinase levels at 1st then drops
- muscle tissue replaced with collagen and adipose
35
Q
Duchenne muscular dystrophy
A
- X linked dystrophin mutation –> absent dystrophin
- faster onset, more severe, most common
- pseudohypertrophy, wheel chair, respiratory problems, cardiomyopathy
36
Q
Becker muscular dystrophy
A
- X linked dystrophin mutation –> some dystrophin
- later onset, less severe, slowly progressive, longer lifespan
