SM_233a: Metabolic Disease Flashcards Preview

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Flashcards in SM_233a: Metabolic Disease Deck (62)
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1

Describe the normal skeletal system

Normal skeletal system

  • 60-70% is inorganic matrix (calcium hydroxyapatite)
  • 30% is composed of organic elements (90% collagen type I) including osteocalcin (most abundant noncollagen protein/important for bone mineralization and acts as serum marker of bone formation and density)
  • Numerous growth factors including osteoblast-activating Transforming Growth Factor beta (TGF-beta) and bone morphogenic protein (BMP)
  • Cellular components: osteoblasts, osteocytes, and osteoclasts

2

Outside of bone is made of _____ bone while inside is made of _____

Outside of bone is made of cortical/lamellar bone while inside is made of spongy/trabecular/cancellous bone

3

Describe intramembranous bone formation

Intramembranous bone formation

  • Develops from collagen (collagen modeled bone)
  • Forms flat bones of skull and clavicles
  • Periosteal osteoprogenitor cells form osteoblasts and responsible for prepubertal thickening of cortex and bone widening (appositional bone growth)

4

Describe enchondral bone formation

Enchondral bone formation

  • Develops from epiphyseal cartilage of the growth plate (cartilage modeled bone)
  • Forms appendicular and axial skeleton and responsible for prepubertal bone lengthening

5

Enchondral bone formation is responsible for development of _____ skeleton 

Enchondral bone formation is responsible for development of appendicular skeleton

 

(perturbations/arrest in normal endochondral ossification lead to many congenital and metabolic bone diseases)

6

____, ____, ____, and ____ stimulate cartilage growth in the zone of proliferation in enchondral bone formation

IHH, PTHrP, BMP, and ILGF-1 stimulate cartilage growth in the zone of proliferation in enchondral bone formation

7

____ inhibits cartilage growth in the zone of proliferation during enchondral bone formation

FGF inhibits cartilage growth in the zone of proliferation during enchondral bone formation

8

_____ and _____ are immature bone

Osteoid and woven bone are immature bone

9

____ is mature bone

Lamellar bone is mature bone

10

Osteoid is ______

Osteoid is unmineralized poorly organized bone matrix (Type I collagen) formed rapidly

 

(immature, becomes adult bone once mineralized)

11

Woven bone is _____

Woven bone is mineralized immature bone formed rapidly and the main component of prepubertal bone

12

Mineralized mature bone forms ____ and has ____ parallel ____ fibers and evenly distributed ____

Mineralized mature bone forms slowly and has parallel collagen type I fibers (lamellae) and evenly distributed osteocytes

13

Cortical (compact bone) involves _____, _____, and _____

Cortical (compact bone) involves collagen first deposited in circumferential lamellae, dissipation of mechanical stress via osteon formation, and collagen deposition around Haversian canals as concentric lamellae

14

Cancellous (spongy) bone is formed by ____ and involves deposition of ____

Cancellous (spongy) bone is formed by enchondral ossification and involves deposition of collagen in longitudinal lamellae

15

Cellular elements of bone are ____, ____, and ____

Cellular elements of bone are osteoblasts, osteocytes, and osteoclasts

16

Describe osteoblasts

Osteoblasts

  • Derived from mesenchymal stem cells & line surface of bone
  • Cell surface receptors include PTH, Vitamin D, estrogen, and others
  • Produce matrix proteins and type I collagen and initiate mineralization

17

Describe osteocytes

Osteocytes

  • Osteoblasts that are incorporated into mature bone (most common cells in bone)
  • Produce sclerostin: protein that inhibits further bone formation until osteocytes are stimulated

18

Describe osteoclasts

Osteoclasts

  • Multinucleated giant cells formed from monocytic progenitor cells in response to RANK-ligand secreted from osteoblasts and bone stromal cells
  • Responsible for bone resorption
  • Located in resorption pits / Howship's lacunae

19

Osteoblasts contain ____, while osteoclast precursors contain ____

Osteoblasts contain RANK-L, while osteoclast precursors contain RANK

 

(binding together activates osteoclast so it can reabsorb bone)

20

Binding of RANK-L from osteoblasts to RANK on osteoclast precursors ____

Binding of RANK-L from osteoblasts to RANK on osteoclast precursors activates osteoclasts so they can reabsorb bone

21

Describe the osteoclast resorption pit

Osteoclast resorption pit

  • Forms a sealed acidified microenvironment in the resorption pits on the surface of bone
  • Ruffled membrane contains H+ ATPase (mutations in H+ ATPase are most common cause of osteopetrosis)
  • HCl mobilizes the mineral phase and proteinase cathepsin K degrades the organic matrix (type I collagen) -> releases minerals and growth factors from bone

22

Mutations in the ____ in the osteoclast resorption pit are the most common cause of osteopetrosis

Mutations in the H+ ATPase in the osteoclast resorption pit are the most common cause of osteopetrosis

23

Balanced interaction between ____ and ____ ensures normal bone structure through appropriate ____ in response to mechanical stress

Balanced interaction between osteclasts and osteblasts ensures normal bone structure through appropriate bone remodeling in response to mechanical stress

24

Bone remodeling is ____

Bone remodeling is a continuous process that dissipates bone stress throughout the life of the individual

25

Bone remodeling in cortical bone involves ____

Bone remodeling in cortical bone involves Haversian system with osteon formation

26

Bone remodeling in cancellous bone involves ____

Bone remodeling in cancellous bone involves activation of osteoclasts and resorption of bone in Howship's lacuna, then reversal of cell type (osteoblasts replace osteoclasts) leading to bone formation

27

Describe osteon formation in cortical bone

Osteon formation in cortical bone

  • Osteons created in response to stress: aggregates of osteclasts form "cutting cones" and resorb bone (primary osteon) -> osteoblasts fill cavity with bone deposited in concentric lamellae
  • Osteocytes within rings of the osteon communicate through dendritic processes and regulate bone remodeling and mineral stores

28

Describe bone remodeling in trabecular bone

Bone remodeling in trabecular bone

  1. Activation of osteoclasts
  2. Resorption of bone in Howship's lacuna
  3. Reversal of cell type to osteoblasts
  4. Bone formation

29

Describe acute osteomyelitis

Acute osteomyelitis

  • Caused mainly by bacterial infection resulting from hematogenous spread, contiguous spread from abscess or ulcer, direct inoculation of organism into bone, and ischemia (vascular insufficiency)
  • Staphylococcus aureus is most common infectious agent
  • Microscopically acute inflammatory cells are initimately associated with non-viable bone 
  • Periosteum/endosteum responds by forming new bone (involucrum, star top) around dead infected bone
  • Managed by surgery and long course antibiotic therapy

30

Categories of bone diseases include ____, ____, ____, ____, and ____

Categories of bone diseases include abnormal matrix, too little matrix, too little mineralization, too much bone resorption, and too little bone resorption

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