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96 Cards in this Set
- Front
- Back
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What genes encode and direct an orderely temporal sequence of bone development?
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Homeobox genes
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Embryogenesis of bone:
cranial-facial skeleton |
cranial neural crest
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Embryogenesis of bone:
axial skeleton |
paraxial mesoderm
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Embryogenesis of bone:
appendicular skeleton |
lateral plate mesoderm
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Genetic abnormalities:
synpolydactyly |
mutation in HOXD-13
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Genetic abnormalities:
Achondroplasia Thanatophoric dwarfism |
FGFR3
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Genetic abnormalities:
OI |
mutations in COL 1A1
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What is this called?
- abnormal migration of mesencymal cells - localized anomales |
Dysostoses
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What is this called?
- global disorder - mutations in regulators of skeletal formation - affect both cartilage and bone |
Dysplasias
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What is this disease?
- failure of closure of spinal column and skull |
craniorachischisis
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What is this disease? What is the cause?
- extra digit in between 3rd and 4th digits and fused together. |
Synpolydactyly: homeobox mutation in HOXD13 transcription factor
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Dysostoses vs. Dysplasia
synpolydactyly |
dysostoses
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What is the cause of these abnormalities?
- synpolydactyly - absent bone - supernumery bones - long, spider-like bones |
homeobox mutations
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What is the underlying cause of achondroplasia?
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- FGFR3 mutation -> constant activation of FGFR3 -> prolonged suppressio of chondrocyte growth
normal: intermittent stimulation of FGFR3 inhibit cartilage proliferation at growth plate |
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What type of genetic abnormality os Thanatophoric dwarfism?
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missense/point mutation of FGFR3 on chromosome 4
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What is this disease?
- micromelia - macrocephaly - small thrax - bowing of extremities - small iliac wings - platyspondy |
Thanatophoric Dwarfism (lethal dwrafism)
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What is this disease?
- blue-gray sclera |
OI, type I-III
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What is this disease?
- brittle bone disease, easily fractured - hearing impairment - normal lifespan |
Type I OI (AD)
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What is this disease?
- severe skeletal deformity - lethal in utero - collagen can't form triple helix |
Type II OI (AR)
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What is this disease?
- brittle bone disease - progressive kyphoscoliosis - hearing defect - dentin defect |
Type III OI (AR or AD): intermediate severity
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What is this disease?
- short stature - brittle bone, moderate fragility - deficient type I collagen synthesis - no blue sclera |
Type IV OI (AD): intermediate severity.
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What is this disease?
- deficient alpha1-hyaluronidase |
Hurler syndrome: type I mucopolysaccharidosis (MPS)
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Describe the pathogenesis of MPS (mucopolysaccharidosis).
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defects in acid hydrolases that degrade dermatan sulfate, hapran sulfate, keratin sulfate -> GAG acculate in cells of many organs.
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Death in MPS patients is mostly due to which organ failure?
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Heart: MPS accumulate in myocytes -> ischemic heart disease
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What is this disease?
- short stature - abnormal chest - abnormality in hyaline cartilage: accumulation of polysaccharide |
MPS
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What is this disease?
- thicken, brittle bone, "marble bone". - no medullary cavity, filled with primaty spongiosa |
Osteopetrosis
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What is this disease?
- carbonic anhydrase deficiency - "marble bone" |
Type II osteopetrosis
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What is this disease?
- anemia - hydrocephaly - cranial nerve deficits - hepatosplenpmegaly - fatal infections |
Osteopetrosis: infantile malignant
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What is the underlying cause of osteopetrosis?
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deficient osteoclast activity
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Describe the pathogenesis of type II osteopetrosis.
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carbonic anhydrase deficiency -> no acidification of resorption pit to break down hydroxyapatite
no renal acidification of urine |
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Are patients with osteopetrosis anemic since marrow space is filled with primary spongiosa that is not hematopoietic?
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Not anemic because of extramedullaty hematopoiesis.
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What should also give to patients on prolonged corticosteroid therapy to prevent bone loss?
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biphosphate
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What is the effect od corticosteroid on bone mass?
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decrease bone mass by increasing bone resorption on boith cortical and trabecular surface.
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What are the contributing factors for senile type osteoporosis? (4)
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- less replication in osteoblasts, less biosynthetic potential
- genetic: low Ca2+, high PTH, low VitD - reduced physical activity - malnutrition |
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Why are postmenopausal women prone to osteoporosis?
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estrogen inhibit IL1,6,TNF thus lower RANK/RANL expression and increase OPG, thus preventing osteoclasts activity.
Loss of estrogen dis-inhibit the action of osteoclasts. |
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What is this disease?
- significant loss of height - lordosis, kyphoscoliosis - multiple compression fractures |
osteoporosis
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What is Paget's disease?
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osteoclasts are hypersensitive to VitD and RANKL -> hyperactivity of osteoclasts
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What are the phases in Paget's disease?
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- osteolytic
- mixed - osteosclerotic |
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What is the genetic predisposition of paget's disease?
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Chromosome 18q
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What is this disease?
- matrix madness: mozaic pattern of cement lines - affect axial skeleton and proximal limb |
Paget's disease
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These are complications of what disease?
- high output heart failure due to hypervascularity - severe secondary OA - chalk stick type fractures - sarcoma of long bone, pelvis, skull, spine. |
Paget's disease
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What is this disease?
- skull: thickened, coarse sclerotic bone with hypervascular periosteum |
Paget's disease
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What is this disease?
- humerus/femur fracture - pain - secondary OA |
Paget's disease
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How can you treat mild symptoms of Paget's disease?
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calcitonin and biphosphate
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List the bone diseases caused by abnormal mineral homeostasis.
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1. Rickets and osteomalacia: defective minerlaization of matrix
2. Hyperparathyroidism: bone loss 3. renal osteodystrophy: bone loss |
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What is this disease?
- VitD deficiency or deficiency in VitD metabolism in kids - softening/weakneing of bone |
Ricket's disease
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What is this disease?
- defective mineralization of matrix during remodeling in adults - |
osteomalacia
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Describe the pathogenesis of bone loss in hyperparathyroidism.
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high PTH -> osteoblast express RANKL -> osteoclasts activated -> bone resorption
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What is this disease?
Morphology: - "brown tumor" - dissecting osteitis X-ray: - "railroad track" osteopenia |
Hyperparathyroidism
- brown tumor: reparative fibrous tissue, hemorrhage, hemosiderin after microfractures |
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A pateint's fracture bone is resected, looking like a brown tumor. What is going on and what can you tell about this person's condition?
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This person has hyperparathyroidism.
brown tumor: reparative fibrous tissue, hemorrhage, hemosiderin after microfractures |
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How does renal failure lead to bone loss? (3 pathways)
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- renal failure -> metabolic acidosis -> bone resorption
- renal failure -> phosphate retention -> hyperphosphatemia -> increase PTH -> osteoclasts activated - renal failure -> decreased conversion of 25-OH D3 to 1,25-OH D3 by kidney -> reduced asborption of Ca2+ from gut -> hypocalcemia -> increase PTH -> osteoclasts activated |
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What happens in the 1st week after bone facture?
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Formation of soft callus
- hematoma - influx of inflammatory cells, fibroblasts, angiogenesis - cytokines activate progenitor cells (osteoblasts and osteoclasts) |
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What happens in the week 2-3 after bone facture?
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Bony callus formation
- deposition of trabecular bone sunperiosteally and in medullary cavity - mesenchymal cells becomes chondroblasts: make cartilage - endochondral ossification: connecting fractured ends |
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What happens in the week 4-6 after bone facture?
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callus remodeling
- excess fibrous tissue, cartilage, bone - bone resorption by osteoclasts and macrophages - callus mineralization for strength |
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What factor may impair bone repair after fracture?
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- deficiency in calcium, phosphate, VitD
- sepsis - diabetes - ischemia |
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What causes delayed union or nonunion in bone repair after fracture?
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too much movement -> more fibrous tissue and cartilage, less bone -> delayed union/nonunion
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What are some common sites in osteonecrosis?
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- medullary cavity (diaphysis, metaphysis)
- subchondral (epiphysis) |
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Subchondral or medullary osteonecrosis:
- chronic pain: initially with activity, then becomes constant - may progress to secondary OA |
subchondral
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Subchondral or medullary osteonecrosis:
- clinically silent - remains stable over time |
medullary
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What is this?
- wedge shaped necrotic area at cartilage surface - intact cartilage layer, may later collapse |
osteonecrosis
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Why is the bony cortex spared in osteonecrosis?
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collateral blood supply
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What are the causes of osteonecrosis?
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ischemia
- frature - corticosteroid - thrombus/embolus - venous hypertension |
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When is medullary osteonecrosis clinically appearant?
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large infarct as in Gaucher's disease, dysbarism, hemaglobinopathies
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What is osteomyelitis?
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inflammation of bone and marrow.
50% cases involves infectious agents. - S. aureus - GNB: in GU infections, drug abusers - H. influenza, GBS: neonates - salmonella: in hemaglobinopathy - T. pallidum |
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What is this disease?
- acute systemic illness: fever/chills, leukocytosis - bone pain - X-ray: elevated periosteum, medullary density |
osteomyelitis in adults
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What is this disease?
- sequestrum: dead bone in medullary cavity - invulucrum: reactive new bone around the sequestrum |
osteomyelitis
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What is this disease?
- soft tissue abscess - draining sinus to skin - acute fever, leukocytosis - pain over bone |
osteomyelitis
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What is this disease?
- supprative arthritis - fever |
osteomyelitis (epiphysis) in kids
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What is this disease?
- spinal deformity - fever - x-ray: elevated periosteum and medullary density |
osteomyelitis in kids (vertebral body)
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Describe the process in which soft tissue abscesses and draining sinus to skin develops in osteomyelitis.
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hematologenous seeding of bone -> acute inflammation → tracks through Haversian canal into periostium → rupture of periosteum -> soft tissue abscess and draining sinus to skin
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In which disease will you see Brodie abscess which is small abscess that involves the cortex and is walled off by reactive bone?
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Osteomyelitis
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What is this disease?
- low grade fever - wt loss - sudden onset of neurologic deficits - kyphoscoliosis - pain with motion |
Potts disease (tuberculous osteomyelitis)
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What is this disease?
X-ray: peduculated mass, continuous with adjacent bone cortex Gross: mushroom-like growth attached by bony stalk Micro: disorganized cartilaginous cap covered by thin layer of fibrous tissue. |
Osteochondroma (benign): chondrogenic
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Name the two types of chondroma.
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1. enchondroma: uniform chondrocytes in medulla of bone, phalanges of hands and feet
2. juxtacortical: surface of bone |
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What is this disease?
X-ray: well circumscribed radioluscent lesion surrounded by thin rim of radiodense bone. Micro: hyaline cartilage with uniform chondrocytes. enchondral ossification at edges. |
chondroma
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What is enchondroma?
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uniform chondrocytes in medulla of bone
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What is this disease?
- multiple enchondromas |
Ollier disease
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What is this disease?
- multiple enchondromas - soft tissue hemangiomas |
Maffuci syndrome
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What is this disease?
X-ray: - well circubscribed - central radiolucency(nidus) with surrounding bone density Micro: - randomly connected trabeculae |
Osteoid osteoma (benign)
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What is this disease?
X-ray: - large well defined lytic defect - erodes subchondral bone at articular surface, cortex often destroyed. - often eccentric Micro: - mononuclear cells in sheets - numerous osteoclasts type giant cells |
Giant cell tumor (benign)
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What is this disease?
Gross: - large, red-brown, focal hemorrhage - cystic degeneration |
Giant cell tumor (benign)
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What is the prognosis of malignant lymphoma?
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depends on stage and subtype: high grade responde well to combined modality therapy with multiagent chemo.
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What is this disease?
X-ray: - ill-defined lytic lesion Micro: - diffuse large B cell lymphoma |
malignant lymphoma
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What is this disease?
X-ray: - nodular growth - endosteal scalloping - fleck of calcification Micro: - too many chdrocytes - wide range of pleomorphism |
chondrosarcoma (malignant): 2nd most common parimary bone sarcoma: age >40
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What is the 2nd most common parimary bone sarcoma?
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chondrosarcoma
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What is the most common parimary bone sarcoma?
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osteosarcoma
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What is the most common site of osteosarcoma?
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Knee 60%
hip15% shoulder 10% |
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Which bone tumor has a bimodal age distribution?
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osteosarcoma:
75% in age<20 20$ in age >60 |
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Which is more common? osteosarcoma or multiple myeloma
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multiple myeloma (blood tumor)
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What is this disease?
X-ray: - infiltrative bone mass invades soft tissue, lifts periosteum - codman triangle: reactive bone |
osteosarcoma
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What is this disease?
Micro: - myxoid matrix - small nuclei, abundant vacuolated cytoplasm |
chordoma
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Which tumor always affect midline bones?
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Chordoma (malignant)
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What genetic defect may cause osteosarcoma?
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mutations in RB gene
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What is this disease?
t(11,22) |
Ewing sarcoma: fusion of EWS gene on 22 with ETS trasnscription factors
PNET |
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What is this disease?
- mostly in teenagers - small blue cell tumor - lytic destructive tumor invading soft tissue |
Ewing sarcoma
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Name the cancers that metastasize into bone.
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- breast
- prostate - thyroid - lung - kidney |
