1. 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. 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. 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. 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. 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. 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. 7. Above: Note the relationship between the compact and spongy bone. Below: Close up of spongy bone.
8. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 23. Components of bone ORGANIC 25% 1. Bone Cells 4% Osteoblasts Osteocytes Osteoclasts 2. Intercellular Matrix 20% Collagens Protein polypeptides Proteoglycans lipids
24. 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. 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. 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. 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. 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. 29. The blue arrows indicate the osteoblasts. The yellow arrows indicate the bone matrix theyve just secreted.
30. 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. 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. 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. 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. 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. 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. 36. www.academic.pgcc.edu/~aimholtz/AandP/LectureNotes/ANP1_Lec/Skeletal/BoneTiss 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. 37. www.academic.pgcc.edu/~aimholtz/AandP/LectureNotes/ANP1_Lec/Skeletal/BoneTiss 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. 38. MEMBRANOUS OSSIFICATION
39. 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. 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. 41. www.academic.pgcc.edu/~aimholtz/AandP/LectureNotes/ANP1_Lec/Skeletal/BoneTiss 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. 42. www.academic.pgcc.edu/~aimholtz/AandP/LectureNotes/ANP1_Lec/Skeletal/BoneTiss 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. 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. 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. 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. 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. 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. 48. www.academic.pgcc.edu/~aimholtz/AandP/LectureNotes/ANP1_Lec/Skeletal/BoneTiss 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. 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. 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. 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. 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. 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. 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. 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. 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. 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
58. 58. Thank you