Basic Science Flashcards by Clint Guitarte

Multifunctional transcription factor that directs transformation of undifferentiated mesenchymal stem cells to osteoblast

RUNX2

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Derived from undifferentiated mesenchymal stem cells

Osteoblasts

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Produced by osteoblast

Type 1 collagen
Alkaline phosphatase
Osteocalcin
Bone sialoprotein
RANKL

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Constitute 90 percent of cells in the mature skeleton

Osteocyte

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Important for control of extracellular calcium and phosphorus concentration, and are less active in matrix production

Osteocyte

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Derived from hematopoietic cells in the macrophage lineage

Osteoclast

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Produced by osteoblast
Binds to immature osteoclasts, and stimulates differentiation into active, mature cells that result in an increase bone resorption

Osteoclast

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Inhibits bone resorption by binding and inactivating RANKL

Osteoprotegerin

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Lysosomal proteolytic digestion enzyme of osteoclast

Cathepsin K

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Osteoclast bind to bone surfaces by means of

Integrins

Vitronectin receptor

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Directly inhibit osteoclastic bone resorption

Bisphosphonate

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How do bisphosphonates inhibit resorption

Inhibiting farsenyl pyrophosphate synthase in the melavonate pathway

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Bone matrix composition

60% inorganic (mineral)

40% organic

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Constitutes the majority of inorganic matrix

Calcium hydroxyapatite

Ca10(PO4)6(OH2)2

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90% of organic component

Type 1 collagen

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Most abundant noncollagenous protein in bone

Osteocalcin

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Law that states that remodeling occurs in response to mechanical stress

Wolff’s law

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Law that states that compressive forces inhibit growth, whereas tension stimulate it

Hueter-Volkmann law

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Three major types of bone formation

Enchondral formation
Intramembranous formation
Appositional formation

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Bone replaces a cartilage model

Enchondral ossification

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Formation occurs without a cartilage model

Intramembranous formation

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Osteoblast lay down new bone on existing bone

Appositional formation

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Supplies the chondrocytes

Groove of Ranvier

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Three stages of fracture repair

Inflammation
Repair
Remodeling

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Closed treatment fracture healing type

Periosteal bridging callus | Interfragementary enchondral ossification

Fracture healing type compression plate

Primary cortical healing

BMP

BMP2 - acute open tibia fractures BMP7 - tibial non union BMP3 - no osteogenic activity

Properties of bome grafts

Osteoconduction Osteoinduction Osteogenic

Osteoconduction

Acts as scaffoLd for bone growth

Osteoinduction

Invilves growth factors that stimulate bone formation

Osteogenic

Contain primitive mesenchymal cells, osteoblasts, osteocytes

Primary hemeostatic regulators of serum calcium

PTH | 1,25(OH2)2 - vitamin D3

Increased serum calcium | Decreased inorganic phosphate

PTH

Age range when bone mass is at its peak

16-25

Most common cause of hypercalcemia

Malignancy

Chronic renal disease | Phosphorus retention and secondary hyperparathyroidism

Renal osteodystrophy

Failure of mineralization

Children - rickets | Adults - osteomalacia

Width of the zone of provisional calcification is increased, which caused physeal widening and cupping

Rickets

Defined as a lumbar bone density of 2.5 or more SD less than the peak bone mass of a healthy 25 y.o.

Osteoporosis

T score

Peak bone mass of a healthy 25 y.o.

Amount of calcium supplement in osteoporosis

1000-1500mg/day

Ascorbic acid deficiency | Decrease in chondroitin sulfate synthesis and ultimately defective collagen growth and repair

Scurvy

Mutation in genes responsible for metabolism and synthesis of type 1 collagen

Osteogenesis imperfecta

Articular cartilage composition

65-80% water (wet weight) 10-20% collagen 10-15% proteoglycan 5% chondrocytes

Master switch | Mesenchymal precursors to chrondrocytes

SOX9

Responsible for myelinating peripheral nerve axons

Schwann cells

Gaps between Schwann cells

Nodes of ranvier

Four transitional tissues of tendon insertion

Tendon Fibrocartilage Mineralized fibrocartilage (sharpey's fibers) Bone

Early tendon healing collagen type

Type 3

Tendon repair timeline

Weakest at 7-10 days | Maximum strength - 6 months

Types of ligament insertion

Indirect | Direct

Superficial ligament fibers insert at acute angles into the periosteum

Indirect insertion

Both superficial and deep fibers insert through ligament, fibrocartilage, sharpey's fibers, and bone

Direct insertion

Collagen nucleus pulposus

Type 2

Collagen annulus fibrosis

Type 1

Infectino of subcutaneous fat and deep fascia

Necrotizing fasciitis Diabetis risk factor Group A beta hemolytic streptococcus in healty individuals

Most sensitive monitor of course of infection

CRP Short half life Dissipates about 1 week after effective treatment

Osteomylelitis 0-4 months

S. Aureus Gram neg bacilli Group b steptococcus

Osteomyleitis 4 months - 21 years

S. Aureus | Group A streptococci

Epiphyseal osteomyelitis

S. Aureus

Osteomyelitis after 21 years

S aureus | Coagulase negative staph

Osteomyelitis patients with sickle disease

S aureus | Salmonella

Osteomyelitis patients with open fracture

S aureus P aeruginosa Gram neg bacilli

Osteomyelitis diabetic

Polymicrobial

Osteomyelitis intravenous drug abusers

S aureus Serratia Pseudomonas

Osteomyelitis meat handlers

Brucella

Osteomyelitis fisherman

Mycobacterium

Septic arthritis 0-3 months

S aureus Enterobacteriaceae Group b strep N gonorrhea

Septic arthritis 3mos-14 y.o.

S aureus S pyogenes H influenza Gram neg bacilli

Septic arthritis sexually active adults

N gonorrhea S aureus Streptococci Gram neg bacilli

Septic arthritis non sexually active adults

S aureus Streptococci Gram neg bacilli

MRI best for contrasting normal and abnormal tissues

T2 (water)

MRI best demonstrates anatomic structure

T1 (fat)

Intensity of internal force | Force/area

Stress | Measured in pascal

Measure of deformation resulting from loading | Change in length/original length

Strain

Measure of material stiffness | Ability to resist deformation in tension

Young's modulus of elasticity

Cierny's anatomic classification of adult chronic osteomyelitis

Medullary Superficial Localized Diffuse A - normal B - local or mild systemic deficiency C - major nutritional or systemic disorder

Site of calcium absorption

Duodenum and jejunum

Amount calcium absorbed and lost

200-300mg absorbed | 150-200mg renal and GI losses

Recommended calcium daily intake 0-6 mos

210mg/day

Recommended calcium intake 6-12mos

270mg/day

Recommended calcium intake 1-3yrs

500mg

Recommended calcium intake 4-8

800

Recommended calcium intake 9-18

1300mg

Recommended calcium intake 19-50

1000mg

Recommended calcium intake >50

1200mg

Effect of PTH on serum Ca and PO4

Increase Ca | Decrease PO4

Effect of Calcitonin on serum Ca and PO4

Decrease Ca | No effect PO4

Effect of Vit D on serum Ca and PO4

Increase Ca | Increase PO4

Types of Osteoporosis

Type 1: post menopausal Type 2: senile (>70) Type 3: secondary

Low Ca, PO4, High ALP, PTH Normal Vit D

Rickets Ca Deficiency

Low or normal Ca Low PO4 High ALP, PTH low Vit D

Rickets vit D

``` High Ca Normal or Low PO4 Normal or high ALP High PTH Normal or high Vit D ```

Primary Hyperparathyroid

High Ca Normal or high PO4, ALP, Vit D Normal or low PO4

Malignancy

Recombinant PTH Paradoxically stimulates bone formation Intermittent dose

Teriparatide

Incorporated into bone in place of Ca Stimulates secretion of OPG Stimulates osteoblasts differentiation

Strontium ranelate

Selective inhibitor of Cathepsin K

Odanacatib

Competitive inhibitor of RANKL

Denosumab | OPG

Direct inhibition of osteoclast activity by binding into osteclast

Calcitonin