1. Chapter 7 Lecture Outline
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2. Bone as a Tissue
Connective tissue with a matrix hardened by minerals (calcium phosphate)
Individual bones consist of bone tissue, marrow, blood, cartilage and periosteum
Continually remodels itself
Functions of the skeletal system
support, protection, movement, electrolyte balances, acid-base balance and blood formation

3. I. Components and Functions of the Skeletal System
A. Support
B. Protection
C. Movement Facilitation
D. Mineral Storage
E. Blood Cell Production
F. Energy Storage

4. II. Macroscopic Structure of Bones
A. Two types of bone
1. compact- dense white osseous tissue
2. spongy- more loosely organized form of osseous tissue
We will discuss differences between compact and spongy bone
Where located
Microscopic anatomy

5. B. Parts of a Long Bone 1. diaphysis 2. epiphysis
3. articular surfaces
4. periosteum
5. endosteum

6. General Features of Bones
1. Shaft (diaphysis) = cylinder of compact bone
marrow cavity (medullary cavity) lined with endosteum (osteogenic cells and reticular connective tissue)
2. Enlarged ends (epiphyses)
spongy bone covered by compact bone
enlarged to strengthen joint and attach ligaments
3. Joint surface covered with articular cartilage
4. Shaft covered with periosteum (sheath)
outer fibrous layer of collagen
inner osteogenic layer of bone forming cells
5. Endosteum-
lines the internal surface of the bone

7. Structure of a Long Bone
Compact and spongy bone
Marrow cavity
Articular cartilage
Periosteum
Epiphyseal plate
=growth plate

8. Structure of a Flat Bone
External and internal surfaces composed of compact bone
Middle layer is spongy bone and bone marrow
Skull fracture may leave inner layer of compact bone unharmed

9. D. Bone Cells 1. Osteogenic cells 2. Osteoblasts 3. Osteocytes
4. Osteoclasts

10. Cells of Osseous Tissue (1)
Osteogenic cells in endosteum, periosteum or central canals give rise to new osteoblasts
arise from embryonic fibroblasts
multiply continuously
Osteoblasts mineralize organic matter of matrix
Osteocytes are osteoblasts trapped in the matrix they formed
cells in lacunae connected by gap junctions inside canaliculi

11. Cells of Osseous Tissue (2)
Osteoclasts develop in bone marrow by fusion of 3-50 stem cells
Reside in pits that they ate into the bone

12. A. Bone Matrix
Matrix is 25% water, 25% proteins (mostly collagen), 50% calcium salts
Calcium salts: mostly hydroxyapatite
(Ca10(PO4)6(OH)2
Combination provides for strength and resilience
minerals resist compression; collagen resists tension
bone adapts by varying proportions

13. Histology of Bone

14. B. Compact Bone
Osteon = basic structural unit= haversian system
central canal =osteonic canal=haversian canal and its lamellae (cylinders formed from layers)
osteocytes connected to each other and their blood supply by tiny cell processes in canaliculi
Perforating canals or Volkmann canals
vascular canals perpendicularly joining central canals

15. B. Compact Bone Haversian canals Volkmann canals (perforating canals)
Osteon = basic structural unit= haversian system
Two types of vascular channels
Haversian canals
Volkmann canals (perforating canals)
vascular canals perpendicularly joining central canals
Not all of the matrix organized into osteons
Inner and outer boundaries of dense bone are organized in circumferential lamellae, run parallel to bone surface

16. Blood Vessels of Bone

17. C. Spongy Bone
Spongelike appearance formed by plates of bone called trabeculae
spaces filled with red bone marrow
no osteocyte is far from blood of bone marrow
Provides strength with little weight
trabeculae develop along bone’s lines of stress

18. Spongy Bone Structure and Stress

19. Bone Marrow
In medullary cavity (long bone) and among trabeculae (spongy bone)
Red marrow like thick blood
reticular fibers and immature cells
Hemopoietic (produces blood cells)
in vertebrae, ribs, sternum, pelvic girdle and proximal heads of femur and humerus in adults
Yellow marrow
fatty marrow of long bones in adults
Gelatinous marrow of old age
yellow marrow replaced with reddish jelly

20. IV. Ossification B. Endochondral Ossification
Replacement of other tissues with bones
A. Intramembranous Ossification -process that forms flat bones (skull, mandible)
B. Endochondral Ossification
-bones are formed from a hyaline cartilage model
-bone tissue forms within the model
-process that forms long and short bones

21. A. Intramembranous Ossification
1. mesenchyme (embryonic connective tissue)
forms a richly vascularized layer with cell-to-cell contact
2. collagen fibers are laid down randomly
forms a gel-like material
3. mesenchymal cells differentiate into osteoblasts
4. new osteoblasts continue to secrete and mineralize matrix
5. trabeculae are formed (ossification centers)
becomes middle of bone
6. vascular mesenchyme condenses to form peri- and endosteum

22. A. Intramembranous Ossification
7. red bone marrow invades spaces between trabeculae
new periosteum develops osteoblasts
-these form trabeculae which grow together to form compact bone on outer surface

23. Intramembranous Ossification 1
Produces flat bones of skull and clavicle.

24. Intramembranous Ossification 2
Note the periosteum and osteoblasts.

25. B. Endochondral Ossification
1. Mesenchyme condenses in shape of future bone
Differentiate into chondroblasts
Develops perichondrium
2. Model grows as chondroblasts divide
Chondroblasts hypertrophy and die
Matrix becomes calcified
3. Perichondrium converts to periosteum
Forms a thin periosteal collar in mid-diaphysis
4. Blood vessels invade model
Carries osteoblasts, osteoclasts, and red marrow to interior of model

26. B. Endochondral Ossification
5. Interior osteoclasts break down calcified cartilage matrix
Interior osteoblasts produce bone matrix of trabeculae, this is primary ossification center
6. Similar events begin to occur in each epiphysis
These are secondary ossification centers
7. As primary ossification center enlarges, early trabeculae are removed to form medullary cavitiy
This becomes populated with red marrow

27. Stages of Endochondral Ossification

28. Primary Ossification Center and Primary Marrow Cavity

29. Secondary Ossification Centers and Secondary Marrow Cavities

30. Fetal Skeleton at 12 Weeks

31. V. Bone Growth and Remodeling
A. Interstitial growth
Growth in length of bones
1. zone of cell proliferation
2. zone of cell hypertrophy
3. zone of calcification
4. zone of bone deposition
B. Appositional growth
Growth in diameter
Occurs by subperiosteal intramembraneous ossification

32. Remodeling
Occurs for four reasons
1. bone growth in length and width
2. changes in use of bone
3. bone tissue turnover-internal remodeling
4. plasma Ca2+ levels

33. V. Bone Growth and Remodeling
Bones increase in length
interstitial growth of epiphyseal plate
epiphyseal line is left behind when cartilage gone
Bones increase in width = appositional growth
osteoblasts lay down matrix in layers on outer surface and osteoclasts dissolve bone on inner surface
Bones remodeled throughout life
Wolff’s law of bone = architecture of bone determined by mechanical stresses
action of osteoblasts and osteoclasts
greater density and mass of bone in athletes or manual worker is an adaptation to stress

34. Hormonal Regulation of Bone Growth and Replacement
A. Growth Hormone
B. Sex steroids
Bone growth especially rapid in puberty and adolescence when surges of GH, estrogen, and testosterone promote ossification
C. Thyroid hormones increased GH
D. Parathyroid hormones
E. Calcitriol
F. Calcitonin

35. Ion Imbalances Changes in phosphate levels = little effect
Changes in calcium can be serious
hypocalcemia is deficiency of blood calcium
causes excitability of nervous system if too low
muscle spasms, tremors or tetany ~6 mg/dL
laryngospasm and suffocation ~4 mg/dL
with less calcium, sodium channels open more easily, sodium enters cell and excites neuron
hypercalcemia is excess of blood calcium
binding to cell surface makes sodium channels less likely to open, depressing nervous system
muscle weakness and sluggish reflexes, cardiac arrest ~12 mg/dL
Calcium phosphate homeostasis depends on calcitriol, calcitonin and PTH hormone regulation

36. Carpopedal Spasm
Hypocalcemia demonstrated by muscle spasm of hands and feet.

37. Hormonal Control of Calcium Balance
Calcitriol, PTH and calcitonin maintain normal blood calcium concentration.

38. Calcitriol (Activated Vitamin D)
Produced by the following process
UV radiation and epidermal keratinocytes convert steroid derivative to cholecalciferol - D3
liver converts it to calcidiol
kidney converts that to calcitriol (vitamin D)
Calcitriol behaves as a hormone that raises blood calcium concentration
increases intestinal absorption and absorption from the skeleton
increases stem cell differentiation into osteoclasts
promotes urinary reabsorption of calcium ions
Abnormal softness (rickets) in children and (osteomalacia) in adults without vitamin D

39. Calcitriol Synthesis and Action

40. Calcitonin (tones down blood Ca2+ levels)
Secreted (C cells of thyroid gland) when calcium concentration rises too high
Functions
reduces osteoclast activity as much as 70%
increases the number and activity of osteoblasts
Important in children, little effect in adults
osteoclasts more active in children
deficiency does not cause disease in adults
Reduces bone loss in osteoporosis

41. Correction for Hypercalcemia

42. Parathyroid Hormone (PTH)
Glands on posterior surface of thyroid
Released with low calcium blood levels
Function = raise calcium blood level
causes osteoblasts to release osteoclast-stimulating factor (RANKL) increasing osteoclast population
promotes calcium resorption by the kidneys
promotes calcitriol synthesis in the kidneys
inhibits collagen synthesis and bone deposition by osteoblasts
Sporatic injection of low levels of PTH causes bone deposition

43. Correction for Hypocalcemia

44. Other Factors Affecting Bone
Hormones, vitamins and growth factors
Growth rapid at puberty
hormones stimulate osteogenic cells, chondrocytes and matrix deposition in growth plate
girls grow faster than boys and reach full height earlier (estrogen stronger effect)
males grow for a longer time and taller
Growth stops (epiphyseal plate “closes”)
teenage use of anabolic steroids = premature closure of growth plate and short adult stature

45. Osteoporosis 1
Bones lose mass and become brittle (loss of organic matrix and minerals)
risk of fracture of hip, wrist and vertebral column
complications (pneumonia and blood clotting)
Postmenopausal white women at greatest risk
by age 70, average loss is 30% of bone mass
black women rarely suffer symptoms

46. Osteoporosis 2
Estrogen maintains density in both sexes (inhibits resorption)
testes and adrenals produce estrogen in men
rapid loss after menopause, if body fat too low or with disuse during immobilizaton
Treatment
ERT slows bone resorption, but increases risk breast cancer, stroke and heart disease
PTH slows bone loss if given daily injection
Forteo increases density by 10% in 1 year
may promote bone cancer
best treatment is prevention -- exercise and calcium intake (1000 mg/day) between ages 25 and 40

47. Spinal Osteoporosis

48. VII. Effect of Exercise on Bone
Increased exercise causes increased mechanical stress on bone
Stimulates remodeling and increased bone mass
Stimulates release of calcitonin
Lack of exercise causes atrophy of bone