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A H A R D S U B J E C T

Bones

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Skeletal System

y 205+ bonesy Associated CT{ Cartilage{ Tendons

i{ Ligaments{ discs

Functions: Bone

y Maintain body shapey Protect internal organs, brain, spinal cordy System of levers for the muscle system to act upony Mineral storage Ca2+ and Phosphorusg py Blood formation: hematopoiesisy Surface features for muscle insertions and origins

Because of hardness difficult to section

y Must decalcify or grind thin

Bone Anatomy

y Diaphysisy Metaphysisy Epiphysis

Proximal/Distaly Epiphyseal liney Periosteumy Compact boney Spongy boney Articular Cartilagey Medullary cavityy Marrowy Nutrient artery

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Compact/Sp0ngy Bone

SHAPES OF BONES

Long

Short

Flat

Irregular

Sutural

sutural bone

irregular bone

flat bone

long bone

Sesamoid

short bone(carpals)sesamoid bone

(patella)

Bone is a connective tissue

y Cells & extracellular matrixy Matrix is mineralized support & protectiony Calcium phosphate in form of hydroxyapatite

crystals

y ~50:50 organic/inorganicy Can decalcify & tie in knotsy Without organic: fragile

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Periosteum covers bones

y (except at articulations cartilage)y Outer fibrous layery Inner, cellular layer with osteoprogenitor cellsy Collagen fibers from ligaments & tendons go intog g g

bone tissue at angle Sharpeys fibers

Endosteum lines bone cavities

y ~ 1 cell layer thick liningy Osteoprogenitor cells line marrow cavity &

trabeculae of spongy bone

Bone Marrow

y Red bone marrow where blood cells are madey As you grow, amount of red marrow doesn't increase

in proportion to bone growth Yellow marrow forms

y Lots o red in sternum, pelvis

A spot of yellow marrow within Roasted bone marrow

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Mature bone

y Osteons (Haversion systems): 4-20 lamellae with central nerve, artery, vein

y Osteocytes trapped in matrix, connected to each other by canaliculi (processes of osteocytes)

y Sometimes chain of 15

Compact Bone

OSTEONS

Canaliculi between Osteocytes

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Osteocytes

y Mature bone cells that sit in lacunaey Gap junctions between osteocytes provide nutrition

(15 cells in a row)

y Maintain bony matrix; long lived cellsy Stimulated by calcitonin (from thyroid); inhibited by

Parathyroid hormone

Osteocyte with Cytoplasmic Extensions

Osteocytes with Canaliculi

Photomicrograph of dried bone ground very thin. The lacunae and canaliculi filled with air deflect the light and appear dark, showing the communication between these structures through which nutrients derived from blood vessels flow.

Collagen at alternating angles in lamellae

Compact Bone

y Osteons or Haversian systems.y Osteons contain blood vessels, lymphatic

vessels, nerves, and osteocytes along with the calcified matrix.

y Osteons are aligned in the same direction along lines of stress - Lamellar bone.

y Osteons in spongy (trabecular) bone only in very thick portions.

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Compact Bone

&

Spongy Bone:

Spongy Bone

y Rarely contains osteons. y trabeculae surrounding red marrow spaces

Spongy bone Bone is continuously remodeled

y Interstitial lamellae are found between osteons and are remnants of previous concentric lamellae

Circumferential lamellae

y Inner & outer circumferences of shaft line rings in tree

Perforating canals (Volkmanns canals)

y Connect osteonal canals to one another

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Blood supply to bone important

y nutrient foramina

Immature Bone

y Develops in fetusy Doesnt have organized lamella nonlamellar,

woven bone

y Relatively more cells/areay Stains darker more ground substancey Adult: tooth sockets,

remodeling

Cells of Bone Tissue Osteogenic cells:

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Osteoprogenitor cells

y From mesenchymal stem cellsy Resting cell that can transform into osteoblastsy Found on inside/outside surfaces of bone, line

osteonal canals and blood vessels in bone

y bone-lining cells separate category in text, said to be from osteoblasts, help osteocytes

y Flattened, elongate nuclei

Osteoblasts

y Synthesize organic components of matrix (collagen, bone matrix proteins)y Collagen forms osteoid: strands of spiral fibers that

form matrix not immediately calcifiedy Influence deposit of Ca++ POy Influence deposit of Ca , PO4y Active vs. inactive osteoblasts (flat/cuboidal)y Estrogen, PTH stimulate activity

Osteoblasts

Photomicrograph of endochondral ossification. In the upper region is a row of osteoblasts with intense cytoplasmic basophilia, a feature to be expected in cells synthesizing a glycoprotein (collagen). Note an osteoblast being captured in the bone matrix (arrow). Between the layer of osteoblasts and the calcified bone matrix is a pale region made of noncalcified bone matrix called osteoid.

Respond to mechanical stimuli

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Osteocytes discussed earlier

y Mature bone cell enclosed in bone matrix

y In lacunae, but communicate with other cells

y Often shrink in preparationy Quiescent, formative, resorptive?

(M: Marrow cavity, Os: osteoid, CB: calcified bone matrix, C: caniculi, L: lamellae)

Osteoclasts

y Derived from monocytes; bone resorptiony Large, multinucleated, motile cellsy Secrete enzymes that digest matrix

Eosinophilia lots of lyososomes

Osteoclasts

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Osteoclast

y Ruffled bordery Clear zone filaments, few other organellesy Basolateral region exocytosis of digested material

Bone Resorption Acid first, then enzymes

Bone remodeling

y Osteoclasts abundant where bone is changingy 5-10% bone / year?{ Vitamin D{ Nutrition{ Physical activity{ Physical activity{ Age, hormones

RemodelingOn this image, the deepest red color is bone while pink represents either fibrocartilage (i.e., collagen within cartilage) or mineralized cartilage. The central clearing represents thep

invasion of bone into calcified cartilage. Osteoblasts are laying down new bone toward the left of the upper boundary of this cavity. Osteoclasts are removing previously-formed bone .

Bone Replacing Cartilage Remodeling Bone

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Internal remodeling

Lamellae deposited periphery inward

X-ray of bone ground to 200 m

y Light = dense (mineralized)y Interstitial lamellae lighty Bone = dynamic!

Skull cavity increases without increasing bone thicknessOsteoblasts and Osteoclasts are at work

Physiologic aspects of bone

y Reservoir for calciumy Blood levels 8.9-10.1 mg/dLy Parathyroid hormone (from parathyroid of course){ Raise blood calcium levels{ Simulates osteoclasts, osteocytes to resorb bone{ Tell kidneys to hold on to calcium, absorb more in gut

y Calcitonin (from thyroid){ Lowers elevated blood calcium levels{ Inhibits osteoclasts

Bone Formation

y 2 Ways to form: Endochondral & intramembranousy With cartilage model or without

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Intramembranous

y 8th week gestation in skull bonesy Skull bones, mandible, clavicle (collarbone)y Bone forms as small, irregular spicules & trabeculaey Over time they connect and form mature boney

Intramembranous Ossification:

Osteoblasts: Endochondral Ossification

y Cartilage modely Cuff of bone forms in midregion bony collary Cartilage cells in center swell, secrete calciumy Calcified cartilage inhibits diffusion, kills cellsg ,y Blood vessels grow in, osteoprogenitor cells move in

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Secondary center of ossification in epiphysisLeaves cartilage epiphyseal plateWhen that cartilage stops growing bone has reached its max. length

Knee of a 6 year old.

Epiphyseal plate of adolescent (white arrow)

Endochondral Ossification Endochondral Ossification

Fractures

y Break in the boney Simple/Compound (open)

infection

y Single: Horizontal, oblique, spiral

y Comminuted >2 bone fragments

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Types of Fracture: Healing in Bone:

1D - Hematoma formation (fibrin mesh)

3D - Inflammation, macrophages remove debris, Periosteum & endosteumrespond with proliferation of

t it llosteoprogenitor cells

1W - Soft callus granulation, matrix.

3-6W - Callus ossification, woven bone

8+W - Re-modeling absorb/deposit, strength, lamellate.

Stages of wound healing

Proliferation

Resolution/ Remodeling

Reepithelialization, Angiogenesis, Fibrogenesis,

Vessel regression, Collagen remodeling

Time after injury

Hemostasis

Inflammation

PMNs, Macrophages, Lymphocytes

Fibrin clot, platelet deposition

1D 3D 1wk 6wk 8wk

Healing in Bone:

Healing in Bone: Bone healing: Callus

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Broken hip really femurOsteoporosis