Bones I Flashcards
RANK pathway (2):
- RANKL on osteoblast and marrow stromal cells
- RANK receptor on osteoclast precursor allows osteoclast generation and survival
M-CSF Pathway (2):
- M-CSF secreted by osteoblast
- M-CSF receptor allows osteoclast generation and survival
WNT/Beta-catenin pathway (3):
- WNT from marrow stromal cells
- LRP5 and LRP6 osteoblast receptor bind WNT protein
- Secrete OPG which blocks RANK
Bone composition (2):
- Calcium hydroxyapatite (mineral portion)
- Organic matrix mostly type 1 collagen
Osteopontin:
Unique to bone, levels parallel osteoblast activity
Alkaline phosphatase:
From osteoblasts, also in liver and placenta
Woven bone (4):
- Random collagen deposition
- Rapid bone growth
- Resists forces all directions
- Always pathologic in an adult
Lamellar bone (3):
- Ordered collagen deposition
- Replaces woven bone
- Stronger than woven bone
Epiphysis:
Distal to growth plate.
Metaphysis:
Beneath growth plate
Diaphysis:
Center of bone
Dysostosis:
- Local* problems in migration of mesenchyme and their condensation.
- Eg. polydactyly/brachydactyly
Dysplasia:
Global defect in regulation of skeletal organogenesis
Cleidocranial dysplasia (6):
- Autosomal dominant
- RUNX2 transcription factor defect
- Short stature
- Abnormal clavicles
- Supernumerary teeth
- Wormian bone
Achondroplasia (4):
- Growth plate defect from paracrine cell defect
- Reduced chondrocyte proliferation in growth plate
- FGFR3 point mutation –> gain of function
- Autosomal dominant
Achondroplasia appearance (5):
- Short stature
- Short proximal limbs
- Normal trunk length
- Enlarged head with bulging forehead
- Depression of root of nose
Thanatophoric dwarfism (6):
- Most common lethal dwarfism
- Cloverleaf skull
- More severe FGFR3 gain of function mutation
- Micromelic short bowed limbs
- Small underdeveloped chest with bell-shaped abdomen
- Diminished chondrocyte proliferation
LRP5 - Gain of function:
Cannot upregulate osteoclasts
- Autosomal dominant osteopetrosis type 1
Osteoprorosis pseudoglioma syndrome (3):
- Inactive LRP5
- Skeletal fragility
- Loss of vision
Osteopetrosis (5):
- Diffuse systemic bone sclerosis
- Bone deposition replaces medullary cavity
- Bulbous long bones
- Narrow neural foramina
- Brittle bones
Osteopetrosis is due to:
Reduced osteoclast bone resorption
- Cannot acidify pit
Autosomal dominant benign osteopetrosis (6):
- Adolescent or adulthood
- Multiple fractures
- Mild anemia
- Hepatosplenomegaly
- Mild cranial nerve defects
- Can be treated with bone marrow transplant
Osteogenesis imperfecta (4):
- Group of type 1 collagen diseases
- Affects other areas rich in type 1 collagen
- Autosomal dominant
- Fragility vs. child abuse
Osteogenesis imperfecta type 1 (5):
- Normal stature with less fractures after puberty
- Blue sclerae from translucency of sclera
- Dentinogenesis imperfecta from dentin defect
- Hearing loss
- Joint laxity
Mucopolysaccharidoses (3):
- Defect in enzymes degrading dermatan sulfate, heparan sulfate and keratan sulfate
- Abnormalities of hyaline cartilage
- Malformed bones
Osteoporosis:
Increased bone porosity and decreased mass
Aging causes of osteoporosis (4):
- Decreased replicative activity of osteoprogenitor cells
- Decreased synthetic activity of osteoblasts
- Decreased biologic activity of matrix-bound growth factors
- Reduced physical activity
Menopausal causes of osteoporosis (4):
- Decreased serum estrogen
- Increased cytokines
- Increased expression of RANK, RANKL
- Increased osteoclast activity
Low turnover variant of osteoporosis:
Senile osteoporosis
High turnover variant of osteoporosis:
Post-menopausal osteoporosis
Secondary osteoporosis (3):
- Hyperparathyroidism
- Corticosteroids
- Immobilization
Brown tumor (3):
- Bone loss due to hyperparathyroidism replaced by fibrovascular tissue
- Microfractures result in hemorrhage and healing
- Granulation tissue and hemosiderin
Paget disease of bone stages (3):
- Osteolytic stage: osteoclast activity
- V-shaped lesion
- Mixed stage: osteolytic and osteoblastic
- Osteosclerotic stage: Mosaic pattern of lamellar bone due to osteoblasts
Paget disease labs (2):
- Increased alkaline phosphatase
- Normal calcium and PO4
Paget disease: bone overgrowth can lead to (4):
- Cranial nerve palsy
- Heavy skull
- Severe secondary osteoarthritis
- Chalk stick-type fracture
Fracture - soft tissue callus (4):
- Hematoma fibrin creates framework
- Influx inflammation, fibroblasts and capillaries
- Osteoprogenitor cells activated
- No rigidity, easily disrupted
Fracture - boney callus (4):
- Woven bone
- +/- cartilage for enchondral ossification
- Maximum girth of callus 3 wks
- Over time remodels to bear full weight
Osteonecrosis (3):
Avascular necrosis
- Infarction of bone and marrow
- Corticosteroids most common cause
- Dead bone/fat replaced by Ca++ salts
Causes of avascular necrosis (6):
- Idiopathic
- Corticosteroids
- Infection
- Dysbarism
- Pregnancy
- Sickle cell disease
Subchondral infarct (2):
- Chronic pain
- Wedge-shaped subchondral bone
Osteomyelitis:
Bone inflammation almost always from infection
Location of pyogenic osteomyelitis by age (3):
- Neonate: metaphysis and/or epiphysis
- Children: metaphysis
- Adult: epiphyses and subchondral bone
Sequestrum:
Dead piece of bone
Brodie Abscess:
Small intraosseous abscess often in the cortex walled off by reactive bone
Involucrum:
Reactive surrounding bone
Potts disease:
TB infection of spine
