1. Dr. CH.ADITYA (D-ortho) DEVELOPMENT, GENERAL STRUCTURE AND
ORGANIZATION AND TYPES OF BONE MODERATORS : DR.C.
RAGHURAM(PROF&HOD) DR.B.RAMESH (PROF & HOD) DR.CH. RAMU
(ASSO.PROF) DR.VENU (ASST.PROF) DR.VAMSHIDHAR REDDY (ASST.PROF)
DR.K. RAVIKANTH (ASST.PROF) DR.SURESH (ASST.PROF)
2. INTRODUCTION The basic structural unit of a human skeleton
is bone Bone is essentially a highly vascular, living, constantly
changing mineralized connective tissue. It is remarkable for its
hardness, resilience and regenerative capacity. Bone consists of
cells and an intercellular matrix bone comprised of a rigid matrix
of calcium salts deposited around protein fibers. Minerals provide
rigidity Proteins provide elasticity and strength
3. Physiology of Bone The dry weight of bone is composed of 65%
to 70% inorganic material 95% of which is calcium and phosphate
solid The main Ca-P solid is crystalline hydroxyapatite
Ca10(PO4)65H2O An amorphous Ca-P solid is present in young, newly
formed bone. Dominant role in calcium homeostasis is played by
constant resorption and deposition of bone minerals.
4. Other internal factors like hormonal (PTH, calcitonin),
renal (tubular reabsorption), and vitamin D metabolites help to
maintain constant plasma concentration. Total Calcium content in
body 1 kg Only 1g is found in plasma and ECF Remainder in skeleton
as phosphates, carbonates and hydroxides. Calcium ion necessary for
- Blood coagulation - Neuromuscular excitability - Muscular
contraction - Essential ion for enzymes
5. Dietary requirement for normal adult 0.65g/day Growing
children and pregnant- 1g/day Dietary sources- milk and milk
products About 200-250 mg absorbed rest lost in faeces Absorption-
vit D, PTH, calcitonin Normal serum ca levels are 8.8 to 10.8 mg/dl
Excretion mainly through kidney- 4oo mg /day adults and 4-6mg/kg in
children
6. STRUCTURE OF BONE Macroscopic structure macroscopically
living bone is white, with either a dense texture like ivory
(compact bone), or honeycombed by large cavities, the bone being
reduced to a latticework of bars and plates (trabaculae) in which
case it is called cancellous, trabecular or spongy bone Compact
bone is usually limited to the cortices of mature bones (cortical
bone ) function is to provide strength. In contrast , cancellous
bone lies chiefly in the interior and particularly in the case of
long bones. Cancellous bones gives additional strength to cortices
and supports the bone marrow
7. Above: Note the relationship between the compact and spongy
bone. Below: Close up of spongy bone.
8. Microscopic structure of compact bone Consists of multiple
cylindrical structural units known as osteons or haversian systems.
named after clopton havers (1691) it contains the following
structures haversian canal Lamellae Lacunae Canaliculi volkmanns
canal osteon The diagram above represents a long bone shaft in
cross-section. Each yellow circle represents an osteon. The blue
represents additional matrix filling in the space between osteons.
The red in the middle is the marrow cavity.
9. OSTEON HAVERSIAN CANAL Each osteon consists of a single
central canal, known as a haversian canal, surrounded by concentric
layers of calcified bone matrix. Haversian canals allow the passage
of blood vessels, lymphatic vessels, and nerve fibers. Each of the
concentric matrix tubes that surrounds a haversian canal is known
as a lamella. All the collagen fibers in a particular lamella run
in a single direction, while collagen fibers in adjacent lamellae
will run in the opposite direction. This allows bone to better
withstand twisting forces.
10. LAMELLAE 1) concentric lamellae are arranged concentrically
around haversian canal 2) Interstial lamellae Lying in between
intact osteons . These fill the gaps between osteons or are
remnants of bone remodeling. 3)Circumferential lamellae are found
at the outer and inner periphery of the cortex
11. Spider-shaped osteocytes occupy small cavities known as
lacunae at the junctions of the lamellae. Hairlike canals called
canaliculi connect the lacunae to each other and to the central
canal. Canaliculi allow the osteocytes to exchange nutrients,
wastes, and chemical signals to each other via intercellular
connections known as gap junctions.
12. VOLKMANNS CANAL These are oblique canals running at right
angles to the long axis of bone. they contain neurovascular bundle
they connect the haversian canal with the medullary cavity and
surface of bone. they are not surrounded by concentric lamellae of
bone Also known as perforating canal
13. Microscopic Structure of Spongy (Cancellous) Bone 1.
consists of poorly organized trabeculae (small needle-like pieces
of bone) 2. with a lot of open space between them. 3. nourished by
diffusion from nearby Haversian canals.
14. Trabeculae are supportive and connective tissue element
which is formed in cancellous bone Trabeculae develop along the
lines of stress Follows wolfs law: states that reaction of living
bone to the mechanical unloading of a bone segment
15. CLASSIFICATION OF BONES Bones classified according to their
shape: A. Long bones consist of a shaft with two ends 1. Examples
include: a. thigh bone = femur b. upper arm bone = humerus B. Short
bones are cube-like. 1. Examples include: a. wrist bones = carpals
b. ankle bones = tarsals
16. C. Flat bones are thin and usually curved. 1. Examples
include: a. most skull bones, b. breast bone = sternum, c. shoulder
blades = scapulae, d. ribs. D. Irregular bones are not long, short,
or flat. 1. Examples include: a. vertebrae, b. auditory
ossicles.
17. E. Sesamoid bones develop within a tendon. 1. The patella
is a human sesamoid bone. F. Wormian bones (or sutural bones) are
tiny bones within the skull that lie between major skull
bones.
18. Bones classified according to structure:
Spongy(cancellous)- consists of intercrossing and connecting
bone(trabaculae) of varying shapes and thickness b/w which spaces
filled with bone marrow Compact- continuous bone mass containing
interconnecting vascular channels of microscopic size.
19. Parts of a Long Bone 1. Diaphysis = shaft a. consists of a
central medullary cavity (filled with yellow marrow) b. surrounded
by a thick collar of compact bone 2. Epiphyses = expanded ends a.
consist mainly of spongy bone b. surrounded by a thin layer of
compact bone 3. Epiphyseal line = remnant of epiphyseal disc a.
cartilage at the junction of the diaphysis and epiphyses (growth
plate)
20. 4. Periosteum = membrane covering the outer surface of bone
two layers 1.fibrous layer- outer thin layer of dense connective
tissue containing fibroblasts 2.osteogenic layer- contains
osteogenic cells a. richly supplied with blood & lymph vessels,
nerves (nutrition): b. Nutrient Foramen = perforating canal
allowing blood vessels to enter and leave bone. c. Osteogenic layer
contains osteoblasts and osteoclasts
21. 5. Medullary cavity = open space containing yellow bone
marrow in the diaphysis of a long bone a. yellow marrow = fat
storage tissue that does not actively produce blood cells 6.
Endosteum = inner lining of medullary cavity a. contains layer of
osteoblasts & osteoclasts 7. Sharpeys fibers Secure periosteum
to underlying bone 8. Articular cartilage = pad of hyaline
cartilage on the epiphyses where long bones articulate or join. a.
"shock absorber"
22. Flat bones 1. covered by periosteum 2. contains a layer of
spongy bone enclosed between plates of compact bone 3. in a flat
bone, the arrangement looks like a sandwich: - spongy bone ,
sandwiched between - two layers of compact bone . *** Hematopoietic
tissue (red marrow) is located in the spongy bone within flat bones
and the epiphyses of long bones. *** Red marrow is
23. Components of bone ORGANIC 25% 1. Bone Cells 4% Osteoblasts
Osteocytes Osteoclasts 2. Intercellular Matrix 20% Collagens
Protein polypeptides Proteoglycans lipids
24. Components of bone Inorganic 65% 1.Crystalline-
hydroxyapatite 2. Amorphous- calcium phosphate 3. Trapped ions-
citrate, fluoride, sodium, magnesium, potassium Water 10% 1.In bone
crystals 2. Extracellular 3. Cellular
25. CELLS OF BONE Cells of bone are embedded in stiff calcified
matrix. the cells are: 1) osteoprogenator stromal cells 2)
osteoblasts which lay down bone 3) osteocytes within bone 4)
osteoclasts 5) bone lining cells on its surface
26. osteoprogenator stromal cells from pluripotent stromal stem
cells from bone marrow and other connective tissue resembles
fibroblasts (mesenchymal origin) Usually differentiate to
osteoblasts 2 types committed (usual) --inducible-forms ectopic
calcification Depending of nature of induction these may
differentiate into fibroblasts, myoblasts, adipose cells,
chondroblasts
27. Components of bone- Cells OSTEOBLASTS bone building cells
15-30 microns,basophilic cuboidal mononuclear cells found in both
the periosteum and endosteum Large, roughly fusiform cells
characterized by abundant cytoplasm staining a deep blue with
H&E beneath the deep layer of periosteum. Abundant rough ER
responsible for synthesis of organic intercellular substance.
Initiate process of calcification
28. Osteoblasts synthesizes organic matters such as 1) type I
and V collagen 2) gamma carboxyglutamic acid (GLA) containing
proteins osteocalcin and GIA protein 3) osteonectin 4) proteases
and growth factor. bears receptors for vit D3 and 1,25(OH)2
vit.D3,which normally inhibits osteoclasts but in presence of
stimulators such as PTH activates osteoclasts to remove osseous
tissue.
29. The blue arrows indicate the osteoblasts. The yellow arrows
indicate the bone matrix theyve just secreted.
30. Components of Bone- Cells OSTEOCYTES Mature bone cells
Derived from osteoblasts which have reduced or ceased matrix
formation Average life upon 25 years Responsible for maintaining
the bone tissue Each osteocyte is in a lacunae , variable space
between the cell and extracellular matrix Yellow arrows indicate
osteocytes notice how they are surrounded by the pinkish bone
matrix. Blue arrow shows an osteoblast in the process of becoming
an osteocyte.
31. OSTEOCLASTS Multinucleated giant cell varying in size n
number of nuclei Cytoplasm pale staining acidophilic and foamy
Formed by fusion of several osteoblasts or from stromal cells of
marrow Function- resorb minerals and intercellular organic
substance Lie where active removal of bone is occuring on surface
in parts termed resorption bays or lacunae of howship
32. Agents stimulating osteoclasts 1) factors from osteoblasts
2) macrophages/lymphocytes 3) decrease in intracellular calcium 4)
parathyroid hormone Survival time approximately 7 weeks
33. BONE LINING CELLS Are flattened epithelium like cells
particularly evident in adult skeleton, found on resting surface of
bone ie: those not undergoing deposition/resorption Lines endosteal
surface of marrow cavity -On Periosteal surfaces - Vascular canals
within osteons Play active role in regulating differentiation of
osteoprogenator cells May secrete collagenase
34. Intercellular matrix Collagen 90% organic matrix Provides
tensile strength to bone Primarily type I collagen Structure Triple
helix fibril Differs from other types of collagen by amino acid
composition and relative insolubility. X-linking decreases
solubility and increases the tensile strength. Proteoglycans
Composed of glycosaminoglycans complexes Partially responsible for
compressive strength of bone.
35. Matrix Proteins Promote mineralization and bone formation
Osteocalcin Produced by osteoblasts Directly related to regulation
of bone density Most abundant non-collagen matrix protein Inhibited
by PTH Activated by 1,25 Vitamin D Can measure in urine or serum as
marker of bone turnover Osteonectin Secreted by platelets and
osteoblasts Possible role in regulation of calcium and/or
organization of mineral within matrix. Osteopontin Cell binding
protein
36.
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Bone Development Osteogenesis (a.k.a. ossification) is the process
of bone tissue formation. Bone first appears after 7th embryonic
week Develops from embryonic mesenchymal tissue The process of
gradual bone formation is known as ossification. these are 2 types
1) endochondral ossification
37.
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Formation of the Bony Skeleton Before week 8, the human embryonic
skeleton is made of fibrous membranes and hyaline cartilage. After
week 8, bone tissue begins to replace the fibrous membranes and
hyaline cartilage. The development of bone from a fibrous membrane
is called intramembranous ossification. The replacement of hyaline
cartilage with bone is known as endochondral ossification.
38. MEMBRANOUS OSSIFICATION
39. MEMBRANOUS OSSIFICATION In this process the bone is laid
down directly in membranous sheets eg: clavicle, bones of face
vault of skull.. The various stages in ossification are as follows:
1) at the site where bone is to be formed the mesenchymal cells
become densely packed and the region becomes highly vascular. 2)
some cells lay down bundle of collagen fibres in the mesenchymal
condensation 3)some more mesenchymal cells come and lie along the
collagen fibres. These cells are called osteoblasts which secrete
gelatinous matrix. the fibres are swollen up. this mass of swollen
fibres and matrix is called OSTEOID. The location in the
40. 4) Under the influence of osteoblasts calcium salts are
deposited in the osteoid and thus one lamellus of bone is formed.
5) Over this lamellus , another layer of osteoid is laid down by
osteoblasts . the osteoblasts move away to line the new layer of
osteoid. In this process some cells are trapped between lamellae
and osteoid and are called osteocytes. The new osteoid is ossified
to form another lamellus. 6) In this way number of lamellae are
laid down one over another and forms trabecular bone. 7) Collagen
is organized as longitudinal or spiral bundles and torns 8) During
these stages mesenchyme condenses on surface to form fibrovascular
periosteum
41.
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The developing bone grows outward from the ossification center in
small struts called spicules. Mesenchymal cell divisions provide
additional osteoblasts. The osteoblasts require a reliable source
of oxygen and nutrients. Blood vessels trapped among the spicules
meet these demands and additional vessels branch into the area.
These vessels will eventually become entrapped within the growing
bone.
42.
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Initially, the intramembranous bone consists only of spongy bone.
Subsequent remodeling around trapped blood vessels can produce
osteons typical of compact bone. As the rate of growth slows, the
connective tissue around the bone becomes organized into the
fibrous layer of the periosteum. Osteoblasts close to the bone
surface become the inner cellular layer of the periosteum.
43. ENDOCHONDRAL OSSIFICATION In this process formation of bone
is preceded by the formation of a cartilaginous model, which is
subsequently replaced by bone eg: bone of limbs (except clavicle),
trunk and base of skull
44. The steps of endochondral ossification are as follows: 1)
at the site where bone is to be formed the mesenchymal cells become
densely packed 2) some mesenchymal cells become chondroblasts and
lay down hyaline cartilage .mesenchymal cells on the surface of
cartilage form a membrane called perichondrium, which is vascular
and contains osteogenic cells 3) in the area where bone formation
is to begin, the cells enlarge considerably.
45. 4)The intercellular substance b/w enlarged chondroblasts
ossified, under the influence of alkaline phosphatase, secreted by
cartilage cells. The nutrition to the cells cut off and they die
leaving behind empty spaces called primary areolae 5) Some blood
vessels of the perichondrium invades cartilaginous matrix. they are
accompanied by osteogenic cells and is called periosteal bud. It
eats the primary areolae and forms large cavities called secondary
areolae 6) The osteoblasts are arranged along the surfaces of
secondary areolae. 7) Osteoblasts lay down a layer of ossein
fibrils embeded in gelatinous matrix (osteoid). The osteoid is
calcified and lamellus of bone is formed. In this way number of
lamellae are laid down one over
46. Bone development begins at the primary center of
ossification and spreads toward both ends of the cartilaginous
model. While the diameter is small, the entire diaphysis is filled
with spongy bone The primary ossification center enlarges
proximally and distally, while osteoclasts break down the newly
formed spongy bone and open up a medullary cavity in the center of
the shaft. As the osteoblasts move towards the epiphyses, the
epiphyseal cartilage is growing as well. Thus, even though the
shaft is getting longer, the epiphyses have yet to be transformed
into bone.
47. Around birth, most long bones have a bony diaphysis
surrounding remnants of spongy bone, a widening medullary cavity,
and 2 cartilaginous epiphyses. At this time, capillaries and
osteoblasts will migrate into the epiphyses and create secondary
ossification centers. The epiphysis will be transformed into spongy
bone. However, a small cartilaginous plate, known as the epiphyseal
plate, will remain at the juncture between the epiphysis and the
diaphysis.
48.
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Growth in Bone Length Epiphyseal cartilage (close to the epiphysis)
of the epiphyseal plate divides to create more cartilage, while the
diaphyseal cartilage (close to the diaphysis) of the epiphyseal
plate is transformed into bone. This increases the length of the
shaft.
49. Epiphysis is the end of a long bone. Diaphysis is the shaft
of a long bone. Epiphyseal plate is the site of bone growth.
Diaphysis Compact bone Osteoblast Directionofgrowth Chondrocyte
Cartilage owth Newly calcified bone Bone gr Dividing chondrocytes
add length to bone. Chondrocytes produce cartilage. Old
chondrocytes disintegrate. Osteoblasts lay down bone on top of
cartilage.
50. Microscopic structure of growth plate Epiphyseal to
diaphyseal end 4 zones 1.Zone of resting cartilage 2.Zone of young
proliferating chondrocytes 3.Zone of maturing chondrocytes 4.Zone
of calcified cartilage.
51. Blood supply of long bones 5-10% of cardiac output Long
bones receive blood from three sources. Nutrient artery
Metaphyseal- epiphyseal system Periosteal system
52. Nutrient artery - Divides into ascending and descending
branch - Each branch sends lateral(radial) oriented arteriolar
branches most of which lead to cortex, others to sinusoids within
marrow,30% marrow 70% cortical capillary beds Terminal branches
anastamose with epiphyseal and metaphyseal vessels to form
medullary blood supply. - Cortical arterioles originating from main
medullary nutrient artery enter cortex some extend longitudinally
and others radially. These branches ultimately form capillaries
within Haversian systems. - Nutrient artery and branches- inner two
thirds or
53. All long bones have one or more nutrient arteries that
enter through the nutrient foramen accompanied by thin walled veins
and myelinated nerve Humerus- single artery, anteromedially at
junction of middle and lower thirds Femur- two nutrient arteries
from profunda femoris, linea aspera. Radius and ulna- nutrient
foramen proximally and directed towards elbow Tibia- from post
tibial artery penetrates posterolateral cortex just below the
oblique line of tibia
54. Venous Drainage Long bones possess a large central venous
sinus transport effluent blood from marrow capillary bed Central
venous sinus emerges from diaphysis as nutrient vein through
nutrient canal Major venous drainage from long bone is into
periosteal venous complex Only 5- 10% of effluent blood leaving by
the way of nutrient vein Most leaves by metaphyseal vessels part of
periosteal venous system
55. Blood flow through the compactum is normally centrifugal
flow , blood entering endosteal aspect from medullary nutrient
system and flowing out through the periosteal surface. In event of
medullary nutrient system interruption, periosteal system provides
reserve supply and flow becomes centripetal.
56. Functions of bone A. Support 1. the bones in legs and
pelvis support the trunk, 2. the atlas (1st vertebra) supports the
skull, etc. B. Protection of underlying organs 1. the skull
protects the brain, 2. the rib cage protects the heart and lungs,
etc. C. Body Movement 1. skeletal muscles attached to bones by
tendon. 2. serve as levers to move bones D. Hematopoiesis All blood
cells are formed in the red marrow of certain bones
57. E. Inorganic Salt Storage 1. bone stores many minerals a.
calcium, b. phosphorus c. others. 2. also a means of calcium
homeostasis F. Energy Storage 1. yellow marrow in the shaft of long
bones 2. serve as an important chemical energy reserve