Connective Tissue

Connective Tissue
Connective Tissue
Connective Tissue
 Most diverse and abundant tissue in the body. Found in skin, membranes, muscles, bones, nerves and all internal
organs.
 Different types of connective tissue are responsible for a variety of functions.
 Highly vascular. Exceptions include cartilage, which is
avascular and tendons, with a scanty blood supply.
 Except for cartilage, connective tissues are supplied with nerves.
Functions
 Holds internal organs together and give them shape.
 Connects tissues to each other;
 Forms a supporting framework for the body
 Transports substances throughout the body.
 Defends us against microbes and other invaders.
 Stores nutrients as fat
Components of Connective Tissue
 Composed of extracellular matrix (ECM) (ground substance and fibers)
in which various connective tissue cells are embedded
 1. Ground substance
 colorless, transparent, gel-like material in which the cells and fibers of
connective tissue are embedded,
 A complex mixture of glycosaminoglycans (mucopolysaccharide),
proteoglycans, and glycoproteins
 Serves as a lubricant, resists forces of compression; facilitates diffusion of

substances, serves as a barrier, holds body fluids.
 May be fluid, semifluid, gelatinous, or calcified.
2. Connective Tissue Fibres
 Collagen fibres – most abundant protein type (& found almost in
all ct.), at least 25 different types exist; consist of the protein
collagen.
Exhibit great tensile strength
Most highly conc in areas of the body where strong support is
needed.
Collagen fibers do not branch
 Reticular fibres – (composed of type III collagen)
 Form a delicate net-like / mesh-like supporting framework in the
liver, lymph nodes spleen & hemopoietic organs,
 stains black with silver.
• Provide support for capillaries, nerve & muscle cells
•
 Elastic fibres – do not form a mesh-work; consists
of protein elastin surrounded by a glycoprotein
fibrillin.
• Thin & small, exhibit branching, when stretched
they return to their original size (recoil)
• Req in areas where stretching without breaking or
distortion is essential for proper functioning of the
organ.
• Lung, skin, bladder, large blood vessels such as
aorta.

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings
NB. The amount, arrangement & conc of these
fibers varies depending on the function of the
tissue or organ.
NB: Scurvy is a disease where defective collagen
formation from lack of vitamin C results in loose
teeth, skin haemorrhages and death.
Marfan syndrome???

Types of Collagen fibre
 Type 1-bones & tendons

 Type 2-cartilage (hyaline & elastic)
 Type 3-reticular fibres
 Type 4-basement membrane
 Type 5- blood vessels

3. Cells of Connective Tissue
 Resident/fixed cells – fibroblasts, fixed macrophages,
adipocytes, mast cells and adult stem cells.
 Wandering/transient cells - lymphocytes, plasma

cells, neutrophils, eosinophils, basophils,
granulocytes, certain macrophages and monocytes.
 NB: Most cell types in loose connective tissue are transient wandering
cells that migrate from local blood vessels in response to specific stimuli.
 Specialized cells produce the extracellular matrix

 Suffixes
-blasts: immature cells, create the matrix
-cytes: mature cells, maintain the matrix
-clasts: break the matrix down for remodeling
Cells of Connective Tissue
 Fibroblasts -(fusiform shaped with slender cytoplasmic process & large oval nucleus),
most abundant, synthesis the fibers (collagen, elastic & reticular) & secretes the ECM
 Macrophage –(irregularly shaped) develop from monocytes, are phagocytic. Fixed
macrophages include alveolar macrophages and splenic macrophages, function is to
ingest bacterial & other foreign mats..
 Plasma cells – are small cells, develop from B lymphocyte. Plasma cells secrete
antibodies.
 Mast cells (round or fusiform shape)– produce histamine and heparin. Histamine
causes dilations of blood vessels as part of the inflammatory response; can bind to,
ingest and kill bacteria. Heparin prevents coagulation of blood
 Adipocytes (fat cells or adipose) – store triglycerides (fats)
Components of connective tissue

Classes of Connective Tissue
Classified into 3 main groups based on varying amount of
cells, fibers and ground substance
Main classes
 1. Embryonic connective tissues
a. mesenchyme
b. mucous
 Mature connective tissues
 2. Connective tissue proper
 3. Specialized connective tissue – Cartilage, Bone, Blood
Some connective tissues (bone, areolar connective tissue, dense irregular

connective tissue, blood) regenerate easily
1.
2.
Matured Connective tissue

Connective tissue proper
3.
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J. TETTEH 12
Embryonic Connective Tissue
 Embryonic connective tissue – There are 2 types.
 Mesenchyme
 Irregularly shaped mesenchymal cells (stellate shaped with cytoplasmic
process) embedded in semifluid ground substance that contains delicate
reticular fibers.
 gives rise to the various connective tissues in the body,
 found in developing embryo and foetus.
 Paucity of collagen fibers is consistent with the limited physical
stress on the growing fetus.
 Mucous (Wharton’s Jelly)
 Widely scattered fibroblasts embedded in viscous, jellylike ground
substance that contains fine collagen fibers
 found in the umbilical cord; its ground substance is frequently referred to
as Wharton’s jelly
Mucous/embryonic connective tissue???

Embryonic Connective Tissue
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J. TETTEH 17
Connective Tissue Proper
 2 subclasses
 Loose connective tissue – few fibers, abundant cells of various types and
ground substance
 Areolar
 Adipose
 Reticular
 Dense connective tissue - abundant fibers, few cells and little ground
substance
 Dense irregular – most common type
 Dense regular.
 Elastic
 Collagenous
Areolar Connective Tissue – A Model Connective Tissue
 Areolar (Loose) connective tissue
 Most widely distributed of all connective tissue types
 More ground substance, abundant fibroblast,
 Less fibers
 Collagen fibers dominate although reticular & elastic
fibers might be present
 Locations
 Underlies epithelial tissue (lamina propria),
 Surrounds small nerves and blood vessels,
 Packages organs - in and around nearly every body
structure
Loose areolar connective tissue

Areolar Connective Tissue
Adipose Tissue
 Consists of adipocytes specialized for storage of fats
 Cytoplasm and nucleus pushed to one side by fat droplet
 Types
 Yellow (White) adipose tissue – most abundant, white at birth and yellows with age; found in
adults.
 Brown adipose tissue (Multilocular) – found in fetus and infant; adults have only small
amounts (in specific areas of body as axillae, neck and near kidneys). Appear darker due to
very rich blood supply and numerous pigmented mitochondria. Generates less ATP but more
heat to maintain proper body temperature.
An obese person has many more blood vessels than does a lean person – this can cause high blood pressure,
since the heart has to work harder.
Liposuction or suction lipectomy?
Addipose connective tissue

Adipose Tissue
Brown adipose tissue
Reticular Connective Tissue
 Description
 network of reticular fibers (thin form of collagen III fiber) and reticular cells
 Location
 Stroma (supporting framework) of liver, spleen, lymph nodes
 Red bone marrow; reticular lamina of basement membrane; around blood vessels
and muscles
 Functions
 Forms stroma of organs;
 Binds smooth muscle tissue cells;
 Filters and removes worn-out blood cells in spleen and microbes in lymph nodes
Reticular connective tissue

Reticular Connective Tissue
Dense Irregular Connective Tissue
• More collagen fibers, thicker & densely packed.
• Less cells (fibroblast), less ground subs. & less elastic
fibers.
• Collagen fibers irregularly arranged or have a random
orientation.
Locations
 Dermis of skin, submucosa of digestive tract,
 Periosteum of bone, perichondrium of cartilage
 Fibrous capsules of joints, lymph nodes, spleen, testes, liver
 Heart valves and fibrous pericardium of heart
 Functions :withstands tension & provides structural
strength.
Dense irregular connective tissue

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings Figure 4.12e
Dense regular connective tissue
• More collagen fibers, thicker & densely packed.
• Less cells (fibroblast), less ground subs. & less elastic
fibers.
• Collagen fibers are regularly arranged in compact parallel
bundles.
• Between the bundles are loose CT containing parallel rows
of fibroblast.
• Required in areas where tensile strength is needed.
• E.g. tendons, ligament & aponeurosis.

Dense regular connective

Dense Regular Connective Tissue
Dense Irregular Elastic Connective Tissue
 Description
 Elastic fibers predominate with fibroblasts between fibers; unstained tissue
is yellowish
 Function
 allows recoil after stretching
 Location
 Lung tissue, walls of elastic arteries, trachea, bronchial tubes, true vocal
cords, suspensory ligaments of penis, some ligaments between
vertebrae
Elastic Connective Tissue
What type of ct?
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J. TETTEH 39
What type of ct?

What type of ct?

What type of ct?

Specialized Connective Tissues
Specialized Connective Tissues

 Cartilage
 Bone
 Blood
Cartilage
 A specialized dense connective tissue composed
I. cells (chondrocytes)
II.highly specialized extracellular matrix (accounts for 95%: fibers & ground substance). Matrix
contains up of 60% to 80% water.
NB. Matrix is solid & firm but flexible.
 Avascular
 Contain large ratio of glycosaminoglycans to type II collagen fibers.
 This permits diffusion of substances bn the blood vessels in the surrounding CT & the
chondrocytes dispersed within the matrix
 Support soft tissues and assists in the development and growth of long bones. They are more
abundant in the embryo than in the adult.
Cells of Cartilage
 Chondrogenic cells – stem cells.
 Chondroblasts – cartilage forming cells, produce and secrete the
extracellular matrix.
 Chondrocytes – mature cartilage cells that are embedded within

lacunae in the matrix, produce and maintain the extracellular
matrix.
 Chondroclasts – associated with cartilage resorption, remove

calcified cartilage which is then replaced by bone.

Types of Cartilage
 Classified into 3 types based on characteristics of their matrix.
 Hyaline cartilage
 Elastic cartilage
 Fibrocartilage
 Fibrocartilage has a sparse blood supply, but hyaline

and elastic cartilage have no capillaries, their cells being nourished by diffusion
through the ground substance.
 Both hyaline cartilage and fibrocartilage tend to calcify and they may even
ossify in old age.

Hyaline Cartilage (hyaline = glassy)
 Most common type of cartilage
 Composed of abundant type II collagen
 Chondrocytes arranged singly or in clusters (isogenous
groups)
 Presence of perichondrium

Hyaline Cartilage
 Function
 Provides support through flexibility and resilience
 Resists repetitive/compressive stress
 Serves as a temporary skeleton in the foetus until it is replaced by bone
 Locations
 Foetal skeleton
 Articular cartilage of typical synovial joint, costal cartilage, epiphyseal
growth plates
 Cartilages of nasal septum of nose, tracheal ring, bronchi, and larynx
(cricoid cartilage, arytenoid cartilage, thyroid cartilage)

Hyaline Cartilage
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings Figure 4.12h
Elastic Cartilage
 Similar to hyaline cartilage but large number of yellow elastic fibers
 Random arrangement of chondrocytes
 Perichondrium present
Elastic Cartilage
Functions
 Maintains shape of structure
 Allows great flexibility/repeated bending (due to elastic fibres)
 Never calcifies
Locations - external ear/pinna, epiglottis, auditory tube and external

auditory canal, larynx (cuneiform and corniculate cartilages)
Elastic cartilage

Elastic Cartilage
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings Figure 4.12i
Fibrocartilage
 Structure intermediate between hyaline cartilage and dense connective tissue
 Chondrocytes arranged in parallel rows either singly or in isogenous groups
between bundles of collagen
 Composed of abundant type I
 all the chondrocytes and lacunae are of similar sizes
 Absence of perichondrium.

Fibrocartilage
Function - Tensile strength and ability to absorb compressive shock
Locations - Anulus fibrosus of intervertebral discs, pubic symphysis,

menisci of knee joint, labrum of shoulder and hip joints

fibrocartilage

Fibrocartilage
Figure 4.12j
Cartilage- perichondrium
Perichondrium is a dense irregular connective tissue that surrounds elastic cartilage and hyaline cartilage (except the articular cartilage)
Consist of outer fibrous layer and inner cellular layer (contain chondrogenic cells and chondroblasts)
Cartilage- perichondrium
unctions
blood vessels in the perichondrium provide oxygen and nutrients, which diffuse into the avascular cartilage
serves as a source of new chondrocytes during appositional growth and repair of cartilage
acts like a girdle to resist outward expansion when the cartilage is subjected to pressure.
Growth of cartilage
 1. Interstitial growth: mitosis of the chondrocytes

within the matrix & the deposition of new matrix
bn the cells.
 Appositional growth: occurs peripherally, thus

chondroblast within the perichondrium
differentiate and add more chondrocytes to the
cartilage peripherally

Growth of cartilage
 A piece of cartilage grows in two ways.
 appositional growth, “surface growth,” –chondrogenic cells in the perichondrium differentiate to
chondroblasts and/or new chondrocytes, which produce the new cartilage tissue by actively secreting matrix.
Growth of cartilage
Interstitial growth, “internal growth” –preexisting chondrocytes within
the cartilage retain the ability to divide and synthesize new matrix, occurs
only during the early stages of cartilage formation, in articular
cartilage and the epiphyseal plates of long bones.
 Cartilage stops growing in the late teens when the skeleton itself stops
growing, and chondrocytes do not divide again. As a result, cartilage
regenerates poorly in adults.
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FOETAL HYALINE
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Growth of cartilage
 Cartilage cells can give rise to benign (chondroma) or malignant
(chondrosarcoma) tumors.
 Hyaline cartilage is more susceptible to degenerative aging processes, eg

Osteoarthritis?
 Under certain conditions, crystals of calcium phosphate precipitate in the matrix of

cartilage. Such calcification is a sign of aging in an adult, but in a child it is a
normal stage in the growth of most bones.
 Note, however, that calcified cartilage is not bone.

Bone
Structure of a Typical Long Bone
 Epiphysis—ends of a bone, contain red
marrow, mostly spongy (cancellous,
trabecular) bone.
 Diaphysis—“shaft” of a bone, made of
compact bone; has a medullary cavity
containing yellow marrow
 Metaphysis—where diaphysis and epiphysis
meet. Has the cartilaginous epiphyseal
(growth) plate, the growing area of a long
bone
 Articular cartilage—a thin layer of cartilage
covering each epiphysis
Commonest site of bone marrow aspiration – manubrium sternum
in adults, iliac crest in children

Periosteum
 Thick layer connective tissue
covering outer surfaces of bones
except at articular surfaces,
sesamoid and ossicles
 Is united to the underlying bone by

collagen (Sharpey’s) fibres
 Are osteogenic. Important in the repair of

fractures, hence bone stripped of its
periosteum will not survive
 Very sensitive to pain cux it has one or more

nerve fibers
 Endosteum
 Thin vascular membrane of connective tissue that
lines the inner surface of the bony tissue that
forms the medullary cavity
 Single layered and lines inner bone surfaces;
covers the trabeculae of spongy bone and also
lines the central canals of osteons
 Osteogenic and contributes to new bone
formation.
Articular
cartilage
Compact bone
Proximal
epiphysis
Spongy bone
Endosteum
Epiphyseal
line
Periosteum Endosteum
Compact bone
Medullary
cavity
(lined by
endosteum) Yellow
Diaphysis
bone marrow
Compact bone
Periosteum
Perforating
collagen fiber
bundles
Nutrient
arteries
Distal
epiphysis
Bone (Osseous tissue)
 Highly vascular
 Consists of
 Organic components (about 35% of the dry weight)
 cells, collagen fibers (95%), and ground substance
 Inorganic (calcified) components (about 65% of the dry

weight)
 composed of calcium, phosphate, bicarbonate, citrate,
magnesium, potassium, and sodium; primarily of
hydroxyapatite crystals, Ca10(PO4)6(OH)2
Bone Cells
 Osteoprogenitor (osteogenic) cells—located in the periosteum and the endosteum,
persist throughout life as stem cells, can be activated later for bone repair of fractures
or other repair.
 Osteoblasts—produce new bone matrix in a process called ossification; become

trapped in a lacunae.
 Osteocytes— mature bone cells housed in a lacunae, non-dividing cells, maintain bone
matrix, cytoplasmic extensions pass through canaliculi in lamellae to connect to other
osteocytes
 Osteoclasts—large, motile, multinucleated cells that resorb

bone (break down bone by secreting hydrochloric acid, which dissolves the mineral
component of the matrix, and lysosomal enzymes, which digest the organic
components) and release calcium and minerals
Structural classification of bones - Gross
Compact (dense) bone - 80% of bone
- Consists of osteons (haversian
systems) with little space between them
- Has no trabeculae or bone marrow cavities
- Composed almost entirely of lamellar
(mature) bone.
- Is the strongest form of bone and
protects, supports & resists stress.
 Osteons are long cylindrical structures that run
approximately parallel to the long axis of the
diaphysis
 Each osteon is composed of calcified matrix arranged
in concentric lamella around the central (Haversian)
canal. The canal contains blood vessels, nerves and
loose connective tissue
Figure 6.7 Microscopic structure of compact bone.
Compact bone Spongy bone
Perforating
Central (Volkmann’s) canal
(Haversian) canal
Endosteum lining bony canals
Osteon and covering trabeculae
(Haversian system)
Circumferential
lamellae
Perforating collagen fiber bundles

Lamellae Periosteal blood vessel
Periosteum
Nerve Osteocyte
within lacuna
Vein
Lamellae
Artery Central canal
Central
Canaliculi canal Interstitial
Osteocyte Lacunae lamella
in a lacuna
 Between lamellae, osteocyte lies in tiny cavities called lacunae. Osteocytes connect to each other by narrow passageways (canaliculi) containing
cytoplasmic extensions of osteocytes.
 Perforating (Volkmann’s) canals lie at right angles to the central canals and connect the blood and nerve supply of the periosteum to that of the
central canals and the marrow cavity.
 Lying between the osteons are groups of incomplete lamellae called interstitial lamellae –
the remains of old osteons that have been cut through by bone remodeling.
 Circumferential lamellae in the external and internal
surfaces of the layer of compact bone -resist twisting of the
entire long bone.
Figure 6.7 Microscopic structure of compact bone.
Compact bone Spongy bone
Perforating
Central (Volkmann’s) canal
(Haversian) canal
Endosteum lining bony canals
Osteon and covering trabeculae
(Haversian system)
Circumferential
lamellae
Perforating collagen fiber bundles

Lamellae Periosteal blood vessel
Periosteum
Nerve Osteocyte
within lacuna
Vein
Lamellae
Artery Central canal
Central
Canaliculi canal Interstitial
Osteocyte Lacunae lamella
in a lacuna
Bone
Compact Bone - Ground Section, unstained
Spongy (cancellous or trabeculae) bone
 Consists of trabeculae surrounding many red bone marrow–filled
spaces
 Does not contain osteons. Lacunae, osteocytes, canaliculi present.
Spongy (cancellous or trabeculae) bone
 Forms most of the structure of short, flat & irregular bones & the interior of the
epiphyses (ends) in long bones
 May consist of either woven or lamellar bone
 Offer resistance along lines of stress, support and protect red bone marrow,
- Make bones lighter for easier

movement.
- In flat bones of the skull, the

spongy part is called diploe
Bone
Trabeculae Bone
Structural classification of bones - Microscopic
 Primary (immature or woven) bone
 first compact bone produced during foetal development and bone repair.
 has a low mineral content; loose arrangement of collagen fibres
 is remodeled and replaced by lamellar bone except in a few places (e.g., tooth sockets, near
suture lines in skull bones, and at insertion sites of tendons) where they persist.
 Secondary (mature or lamellar) bone

 is the compact bone of adults,
 has a calcified matrix arranged in regular layers,
 the structural units of lamellar bone are called osteons or haversian systems.
Bone Development
The process by which bone forms, called ossification, occurs in 4
principal situations:
1.the initial formation of bones in an embryo and fetus;
2.the growth of bones during infancy, childhood, and
adolescence until their adult sizes are reached;
3.the remodeling of bone (replacement of old bone
by new bone tissue throughout life); and
4.the repair of fractures (breaks in bones) throughout life.
Bone Development
 Osteogenesis (or ossification) - bone formation
 Bone development begins during the 6-8th week of embryonic development.
 2 processes result in bone formation:
 Intramembranous ossification - direct formation of bone within
mesenchyme, embryonic connective tissue. Process forms most flat bones of
skull, mandible, sternum and clavicle. The clavicle is the 1st bone to ossify
but the last bone to fuse
 Endochondral ossification – formation of bone within hyaline cartilage that
develops from mesenchyme.
 Stages of bone development
 Formation of unmineralised intercellular matrix (osteoid)
 Mineralisation of matrix (calcification).
Bone Development
BONE DEVELOPMENT
 Begins in the embryo by 2 distinct process:
1.Intramembranous ossification
2.Endochondral ossifications
NB; Bones produced by these 2 methods do not

differ histologically.

INTRAMEMBRANOUS OSSIFICATION
 Bones devps. From the CT mesenchyme.

 Some cells differentiate directly into osteoblasts & produce
the bony matrix.
 E.g. madible, maxillae, clavicles, sternum & most of the
flat bones of the skull.
 NB. In the dvping. skull, the center of bone dvpt grow
radially, replace the ct & then fuse.
 In neonates, the fontanellels in the skull are the soft
membranous regions where ossification of the skull bones
has not yet been completed.
INTRAMEMBRANOUS OSSIFICATION
 Thus, in IMO, bone dvpt takes place within the richly
vascularized condensed mesenchyma ct. where the
mesenchymal cells differntiate into osteoblasts & produce
primary or immature bone matrix.
 This deposition of immature bone is followed by
remodeling leading to the formation of secodary or matured
bone.

ENDOCHONRIAL OSSIFICATION
 Condensation of mesenchyma cells first give rise to a

hyaline cartilage model of the bone.
 Thus, each bone is preceded by a temporary hyaline
cartilage model.
 Bone tissues slowly replaces most of the cartilage model.
 The cartilage matrix within the center of the cartilage
model begin to calcify & the chondrocytes hypertrophy &
mature.
 As the cartilage calcifies, diffusion of nutrients & gases
thru the calcified matrix decreases.
 The chondrocytes die and the fraagmented calcified matrix

serve as a structural framework for the deposition of the
dvping bone.
 Ostgeoprogenitor cells & blood vessels surrounding ct
penetrate & invade the degenerating cartilage model.
 Osteoprogenitor cells proliferate & give rise to osteoblasts.
 Mesenchymal tissue, osteoblasts & blood vessels form an
ossification (primary) center in the center of the devpin
bone (diaphysis).
 Osteoid matrix is then produced & mineralised into a
bone .
 Expansion of the ossification center replaces the

cartilage model with bone except over the free
ends (epiphysis) of the long bones.
 Thus, a layer of hyaline cartilage covers the ends

of the bone as the articular cartilage.

Bone Development
Bone Development
Bone formation (ossification)
 The site where bone first forms is the primary centre of
ossification. Appear 7-12th week in the middle of the
diaphysis.
 Cartilage degenerates, leaving cavities that merge to form the
medullary cavity. Osteoblasts lay down bone. The epiphyses remain cartilaginous and only acquire
secondary ossification centres much later, usually after birth.
 Bone replaces cartilage, except for the epiphyseal (growth) plate. The growing end of the diaphysis
is the metaphysis, and the adjacent epiphyseal cartilage is the epiphyseal (growth) plate.
 The thickness of the epiphyseal plate does not change during childhood. As the long bone
grows, bone is added to the diaphyseal end of the epiphyseal plate.
Bone formation (ossification)
 Damage of the epiphyseal plate, particularly at the growing end, following fracture of a long bone
in child may lead to shortening of the limb.
 When ossification occurs across the epiphyseal plate, the diaphysis and epiphysis fuse and bone
growth ceases, leaving epiphyseal line (about 18 years in females and 21 years in males). Estrogen
influences the closure of the epiphyseal plate of bones
 Bone grows in thickness or diameter due to the addition of new bone tissue by periosteal
osteoblasts around the outer surface of the bone (appositional growth). Long
bones lengthen by the addition of bone material on the diaphyseal side of the epiphyseal plate by
interstitial growth.
Bone Modeling and Remodeling
 Osteoclasts and osteoblasts often work together to reshape

bone (modeling) and replace old bone with new bone
(remodeling).
 In bone modeling the osteoclasts and osteoblasts work on
opposite surfaces of bone to position the bone in one direction.
 In bone remodeling, osteoclasts and osteoblasts work on the

same surface of bone to digest old bone and replace it with new
bone.
Role of vitamins in bone formation
 Dietary minerals (especially calcium and phosphorus) and vitamins (A, C, D, K, and B12)
are needed for bone growth and maintenance.
 Vitamin D - necessary for absorption of calcium and bone formation. Deficiency results in
poorly calcified (soft bone, a condition known as rickets in children and osteomalacia in
adults). Excess of vitamin D causes bone resorption.
 Vitamin A - Deficiency inhibits proper bone formation and growth, whereas an excess
accelerates ossification of the epiphyseal plates. Deficiency or excess of vitamin A results
in small stature.
 Vitamin C - necessary for collagen formation. Deficiency results in scurvy, characterized

by poor bone growth and inadequate fracture repair.
Role of hormones in bone formation
 Parathyroid hormone increases blood Ca2+ level by promoting bone resportion, whereas
calcitonin suppresses mobilization of calcium from bone (decreases blood Ca 2+ level) .
 Insulin-like growth factors (IGFs), human growth hormone, thyroid hormones, and insulin
stimulate bone growth.
 Sex hormones slow resorption of old bone and promote new bone deposition.
Exercise and Aging
 Estrogen decline in postmenopausal women increases their risk of bone loss.
Estrogen replacement therapy is associated with increased risk of heart attack,
stroke, and breast cancer.
 Weight-bearing activities stimulate osteoblasts and, consequently, help build

thicker, stronger bones and
retard loss of bone mass that occurs as people age.
Vitamin D Deficiencies
 Osteomalacia and rickets
result from inadequate
mineralization of bone.
 Rickets: lack of Vitamin D in

children causing bowing of the
skeleton
 Osteomalacia: lack of vitamin

D in adults due to a poor diet,
softening of the bones.
Osteoporosis
 Abnormal loss of bony tissue
resulting in fragile porous bones
attributable to a lack of calcium;
most common in postmenopausal
women
 Bone cells become less active due

to estrogen loss, bone resorption
outpaces bone formation.
 Increased susceptibility to fractures

of the hip and wrist, vertebral
compression, loss of body height
and development of kyphosis
 Osteopenia is a decreased calcification of bone or a reduced bone mass due to an
inadequate osteoid synthesis.
 Albers-Schonberg disease (Osteopetrosis): An inherited disorder characterized by an

increase in bone density; in severe forms the bone marrow cavity may be obliterated. Occur
due to defective resorption of immature bone.
 Osteophyte (Bony spur): Small abnormal bony outgrowth.
 Achondroplasia (dwarfism): Do occurs due to defective endochondral ossification.

Paget’s disease (Osteitis deformans):
 There is an excessive proliferation of osteoclasts so that bone
resorption occurs faster than bone deposition.
 In response, osteoblasts attempt to compensate, but the new bone

is weaker because it has a higher proportion of spongy to
compact bone, mineralization is decreased, and the newly
synthesized extracellular matrix contains abnormal proteins.
 The newly formed bone, especially that of the pelvis, limbs,

lower vertebrae, and skull, becomes enlarged, hard, and brittle
leading to bone pain and fractures and skeletal deformities.
Paget’s disease (Osteitis deformans):
Muscle Tissue
Muscle Tissue
Muscle Tissue
 Specialized for contraction.
 Functional features
 Contractility
 Long cells shorten and generate pulling force
 Excitability
 Electrical nerve impulse stimulates the muscle cell to contract
 Extensibility
 Can be stretched back to its original length by contraction of an opposing muscle
 Elasticity
 Can recoil after being stretched
Muscle Tissue
Functions of muscles
Producing motions.
Stabilizing body positions.
Storing and moving substances within the body.
Generating heat (thermogenesis)
Classification of Muscle Tissue
 Structurally, muscles are classified according to the

appearance of the contractile cells containing thin
filaments (actin) and thick filaments (myosin) into:
 Striated muscles -cells exhibit cross-striations at
the light microscope level
 Skeletal muscle tissue
 Cardiac muscle tissue
 Smooth muscle -cells do not exhibit cross-
striations.
Classification of Muscle Tissue
 Functionally,
 Voluntary
 Skeletal muscle
 Involuntary
 Cardiac and smooth muscles
 Have the intrinsic ability to initiate contraction
 Contraction is stimulated by autonomic nerve
impulses, some hormones and local metabolites.
3 Types of Muscle Tissue
 Skeletal muscle
 attaches to bone, skin or fascia
 striated with light & dark bands visible with scope
 voluntary control of contraction & relaxation
Thomas Diby 10-125

Skeletal Muscle Tissue
 Long, cylindrical cells, non-branching fibres
 Multinucleated (several nuclei)
 Peripheral nuclei
 Striation
Skeletal muscle fibers cannot divide and have limited powers of regeneration. Satellite cells between the plasma
membrane of a mature skeletal muscle fiber and its external lamina enables repair of damaged muscle fibers.
Skeletal muscle fibers form by the fusion of many myoblasts, hence are multinucleated.
Thomas Diby 10-128
Connective Tissue Sheaths in Skeletal Muscle
Epimysium – dense regular
connective tissue that
surrounds the entire muscle.
The major vascular and
nerve supply of
the muscle penetrates the
epimysium
Perimysium – connective tissue

that surrounds a group of muscle
cells to form a fascicle
Endomysium – thin layer of connective tissue that

surrounds each muscle cell
Basic Features of a Skeletal Muscle
Connective tissue sheaths are continuous with tendons (attach muscles
to bones). A flat tendon is called aponeurosis. A fascia is a dense
irregular connective tissue that lines the body wall and limbs and holds
functional muscle units together. A subcutaneous tissue separates
muscle from the skin.
 Functions
 Contraction is usually under voluntary or conscious control.
 Facial expression
 Movement, maintains posture, stabilizes joints, and
generates body heat.
 Locations
 Skeletal muscles attached to bones (occasionally to skin, for
instance the muscles of the face involved with expression); also
found in the tongue, pharynx and upper part of the esophagus
 Cardiac muscle
 striated in appearance
 involuntary control
 autorhythmic because of built in pacemaker
Thomas Diby 10-132

Cardiac Muscle Tissue
 Broader, shorter branching fibres
 Generally uninucleated (single central nucleus), some cells binucleated.
 Uninucleated that interdigitate at specialize junctions kn as
 Intercalated discs (Present)
 Cross-striations
 No regenerative activity (normal condition)
 Able to generate their own action potentials; they do not require nerve impulses
to contract.
Anatomy of Cardiac Muscle
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 Striated , short, quadrangular-shaped, branching fibers

 Single centrally located nucleus
 Cells connected by intercalated discs with gap junctions
 Same arrangement of thick & thin filaments as skeletal
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings Figure 4.14b
 Intercalated discs
 specialized intercellular junctions connecting one cardiac muscle fibers to another
 allow the electrical activity of one cardiac muscle cell to spread quickly to
adjacent muscle cells. Cells do not need to be stimulated individually
 Function
 Involuntary. Contracts to propel blood into circulatory system
 Location
 Occurs in myocardium of heart
Thomas Diby 10-139
 Smooth muscle
 attached to hair follicles in skin
 in walls of hollow organs -- blood vessels & GI
 nonstriated in appearance
 involuntary
Thomas Diby 10-140

Smooth Muscle Tissue
 Narrow, spindle-shaped cells usually lying parallel
 Single central nucleus
 No striations
Functions
 Specialized for slow, prolonged contraction.
 Propels substances along internal passageways.
 Capable of dividing to maintain or increase their number
 Location
Mostly walls of hollow organs (gut, genitourinary renal system, vessels), intrinsic muscles of
eye
Thomas Diby 10-143
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Muscle Fiber or Myofibers
 Muscle cells are long, cylindrical & multinucleated

 Sarcolemma = muscle cell membrane
 Sarcoplasm = (cytoplasm) : filled with tiny threads called myofibrils &
myoglobin (red-colored, oxygen-binding protein)
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Transverse Tubules
 T (transverse) tubules are invaginations of the sarcolemma into

the center of the cell
 filled with extracellular fluid
 carry muscle action potentials down into cell
 Terminal cisternae: stores calcium
 Mitochondria lie in rows throughout the cell
 near the muscle proteins that use ATP during contraction
Myofibrils & Myofilaments
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 Muscle fibers are filled with threads called myofibrils

separated by SR (sarcoplasmic reticulum)
 Myofilaments (thick & thin filaments) are the contractile
proteins of muscle
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Sarcoplasmic Reticulum (SR)

y
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1
4
8
 System of tubular sacs similar to smooth ER in

nonmuscle cells
 Stores Ca+ 2 in a relaxed muscle
 Release of Ca+ 2 triggers muscle contraction
Filaments and the Sarcomere
 Thick and thin filaments overlap each other in a

pattern that creates striations (light I bands and dark
A bands)
 They are arranged in compartments called
sarcomeres, separated by Z discs.
 In the overlap region, six thin filaments surround
each thick filament
Thomas Diby 10-149

Disorders of Muscle Tissue
 Muscle tissues experience few disorders
 Heart muscle is the exception
 Skeletal muscle - remarkably resistant to infection
 Smooth muscle - problems stem from external irritants
 Muscular dystrophy
 A group of inherited muscle destroying disease
 Affected muscles enlarge with fat and connective tissue
 Muscles degenerate
 Types of muscular dystrophy
 Duchenne muscular dystrophy - a sex-linked recessive disease.
 Myotonic dystrophy - skeletal-muscle spasms followed by muscle weakness and abnormal heart
rhythm
Disorders of Muscle Tissue
Fibromyositis (or firomyalgia)

a group of conditions involving chronic inflammation of a muscle,
its connective tissue coverings and tendons, and capsules of nearby
joints.
Symptoms are nonspecific and involve fatigue, frequent awakening
from sleep, severe musculoskeletal pain, and headache
 Affects mostly women
Muscle Tissue Throughout Life
 With increased age

 Amount of connective tissue increases in muscles
 Number of muscle fibers decreases
 Loss of muscle mass with aging
 Decrease in muscular strength by 50% by age 80
 Sarcopenia – muscle wasting
What are the meaning of the following terms: myalgia and

myopathy, dysplasia, hypertrophy and hyperplasia?
Nervous System
Overview of Nervous Tissue

Nervous Tissue
Learning outcomes
Define neuron, describe its structural components, and relate each structure to its functional role.
Describe the structure of a synapse.
Classify neurons both structurally and functionally.
List the six types of neuroglia and distinguish them by location and function.
Describe the structure of myelin sheaths
Distinguish gray matter from white matter.
Define nerve and describe the structural components
of nerves
NERVOUS SYSTEM
 Is a complex network of
nerves and cells that carry
messages to and from the
brain & spinal cord to
various parts of the body.

Basic Divisions of the Nervous System
1. Central nervous system
(CNS)
 Brain and spinal cord
 Integrating and command
center
 Protected by bones, CSF and
meninges
2. Peripheral nervous system
(PNS)
 Outside the CNS; Consists of
 Cranial and Spinal nerves
 Associated ganglia – sensory
ganglia, cranial nerve ganglia,
autonomic ganglia
NERVOUS SYSTEM

Cells of the Nervous System
 Two main cell types

 Excitable cells/Neurons/Nerve cells – transmit
electrical signals
 Nonexcitable/ Supporting cells (neuroglial cells,
glial cells)
 Glial cells have branching processes and a central cell body
 Outnumber neurons 10 to 1
 Make up half the mass of the brain
 Can divide throughout life
What is glioma?
The Neuron / Nerve cell
 Basic structural and functional unit of the nervous system.
 Other special characteristics

 Longevity – can live and function for a lifetime
 Amitotic– cannot be replaced if they are destroyed (in most
circumstances). Neurons that can be replaced include the
olfactory epithelium of the nose and certain regions of the
hippocampus in the brain, which is involved in memory.
 High metabolic rate – require abundant oxygen and glucose.
Neurons die after 5 minutes without oxygen
Nervous Tissue
 All neurons are
characterized by
 a cell body/soma and
 2 types of processes:
I. one axon, which
transmits a nerve impulse
away from the cell body,
and
II.one or more dendrites,
which carry impulses
toward the cell body.
Structure of a Typical Large Neuron
Nervous Tissue
Neuron
The Cell Body (soma, perikaryon)
 The metabolic center of the
neuron
 5 - 140 μm in diameter
 Contains usual organelles
plus other structures
 Chromatophilic bodies
(Nissl bodies)
 Clusters of rough ER and
free ribosomes
 Stain darkly and renew
membranes of the cell
 Neurofibrils – bundles of
intermediate filaments
 Form a network between
chromatophilic bodies
The Cell Body (soma, perikaryon)
In certain neurons, the cell body may contain pigments
such as black melanin, a red pigment that contains
iron, or a gold-brown pigment called lipofuscin.
Most neuronal cell bodies are located in the CNS and are
protected by the bones of the skull and vertebral column
Terminologies
 Nuclei are clusters of cell bodies in the CNS, whereas
ganglia are clusters of cell bodies in the PNS, which
lie along peripheral nerves.
 In the CNS, bundles of neuron processes are called tracts. In the PNS, these
bundles are called nerves.
 Nerve impulses are actually electrochemical changes

transmitted by neurons to other neurons and to cells
outside the nervous system
Neuron Processes- Dendrites
 Extensively branching from
the cell body
 Function as receptive sites
for receiving signals from
other neurons
 Transmit electrical signals
toward the cell body
 Chromatophilic bodies –
only extend into the basal
part of dendrites and to the
base of the axon hillock
Neuron Processes-Axons
 a long slender extension from the
soma, Emerges from the soma at the
'axon hillock'
 Each neuron has only one axon. Some
axons have occasional branches
known as axon collaterals,
 Axons may be myelinated or
unmyelinated
 Chromatophilic bodies are absent. No
protein synthesis in axon
 Have the same organelles as dendrites, except for rough
endoplasmic reticulum and a Golgi apparatus.
 Decay quickly if they are cut or experience severe damage
 Impulse generator and conductor; transmit impulses away
from the cell body
 Multiple branches at the end
known as terminal branches
(telodendria)
 Terminal branches end in
knobs called axon terminals
(also synaptic terminals,
synaptic knobs, synaptic
boutons, or terminal boutons).
 Axon terminals contain
synaptic vesicles, specialized
in releasing
neurotransmitters
Synapses
 Are the sites of functional contact of a neuron with another neuron, an effector cell,
or a sensory receptor cell
 Signals pass across synapse in one direction
 Presynaptic neuron - Conducts signal toward a synapse
 Postsynaptic neuron - Transmits electrical activity away from a synapse
 Synaptic vesicles on presynaptic side
 Membrane-bound sacs containing neurotransmitters
 Synaptic cleft - The actual gap between neurons; Separates the plasma membrane of
the two neurons (Pre and postsynaptic neurons)
 A synapse between a neuron and a muscle cell is known as a neuromuscular junction.
Two Neurons Communicating at a Synapse
Types of Synapses
 Axodendritic
 Between axon terminals of one neuron and
dendrites of another
 Most common type of synapse
 Axosomatic
 Between axons and neuronal cell bodies
 Uncommon types of synapses: Axoaxonic,
dendrodendritic, and dendrosomatic
Structural classification of Neurons
 According to the number of processes extending from the cell
body
1. Multipolar neurons
Numerous dendrites
and one axon
Most abundant type –
about 99%
Classification of Neurons
2. Bipolar neurons
Rare neurons
One dendrite and one axon
Found in some special
sensory organs (inner ear,
olfactory epithelium of the
nose, retina of the eye),
where they mostly serve as
sensory neurons
Classification of Neurons
3. Unipolar (pseudounipolar)
neurons
Cell bodies in ganglia outside
the CNS
The central process runs
centrally into the CNS
The peripheral process extends
peripherally to the receptors
 Start as bipolar neurons during
development
 Are sensory neurons of the

PNS and found in spinal and
cranial nerve ganglia.
Functional Classification of Neurons
 According to the direction the nerve impulse travels
1. Sensory (afferent) neurons

 Transmit impulses from tissues and organs toward the CNS
 Virtually all are unipolar neurons
2. Motor (efferent) neurons

 Carry impulses away from the CNS to effector organs
 Most motor neurons are multipolar
 Cell bodies are within the CNS
 Form junctions with effectors (muscles and glands)
Functional Classification of Neurons
 Has two branches:
 Somatic motor neurons innervate skeletal muscles.
 Visceral motor neurons (ANS) innervate smooth and
cardiac muscle, glands
3. Interneurons (association neurons)

 Most are multipolar
 Lie between motor and sensory neurons; confined to the CNS
 Make up 99.98% of the neurons of the body
Neurons Classified by Function
Neuroglial cells/Supporting Cells/Glial cells
 6 types of supporting cells
 4 in the CNS
 Astrocytes
 Microglia
 Ependymal cell
 Oligodendrocytes
 2 in the PNS
 Satellite cells
 Schwann cells
General functions of Supporting Cells/Glial cells
 Surround neurons and hold them in place
 Supply nutrients and oxygen to neurons
 Insulate one neuron from another
 Destroy and remove the carcasses of dead neurons (clean up)
 Repair of neuronal injury,
 Regulate of the internal fluid environment of the CNS,
 Clearance of neurotransmitters from synaptic clefts,
 Metabolic exchange between the vascular system and the neurons of the nervous
system.
Neuroglia in the CNS
 Astrocytes
 star-shaped, largest and most abundant glial cell type
 usually found between neurons and blood vessels, where they anchor
these components together
 contribute to the formation of the blood-brain barrier, to isolate the
CNS from the general circulation.
 control volume of blood flow through capillaries
 absorb and recycle certain neurotransmitters
 involved in synapse formation in developing neural tissue
 produce molecules necessary for neuronal growth (BDTF)
 regulates sodium ion, potassium ion, and carbon dioxide concentrations
 Microglia
 smallest and least
abundant glial cell
 Phagocytes – the
macrophages
of the CNS
 appear early in embryonic
development.
 Derived from blood cells
called monocytes
 Ependymal cells
 Line the central canal of the spinal cord and
ventricles of the brain
 Help form choroid plexuses that secrete
cerebrospinal fluid (CSF)
 Bear cilia – help circulate the CSF
 Oligodendrocytes (“few-branch cells.”)

 Form the myelin sheaths around axons in the CNS
 Have multiple processes
 Coil around several different axons
Neuroglia in the PNS
 Satellite cells (amphicytes) – have similar functions to the astrocytes of the
CNS; surround and protect neuron cell bodies within ganglia.
 Schwann cells (neurolemmocytes)

 Form myelin sheath and neurolemma (sheath of Schwann) around axons
in the PNS. Surround only one axon.
 Neurolemma is the superficial cytoplasmic covering provided by Schwann
cells. It provides a regeneration tube that guides regrowth of a severed
axon

Myelin Sheaths
 Myelin is multilayered lipids and proteins that form a sheath around certain nerve fibers
 Is formed by oligodendrocytes in the CNS and Schwann cells in the PNS
 Form an insulating layer
 Prevent leakage of electrical current from the axon, and
 Increase the speed of impulse conduction
 Surround thicker axons. Thin axons are unmyelinated and conduct impulses more
slowly
Multiple sclerosis is demyelination disease

Myelin Sheath of PNS
Myelin Sheaths in the PNS
 Myelin sheaths in the PNS are not continous

 Nodes of Ranvier – gaps along axon
Gray and White Matter in the CNS
 Gray matter
 contains neuronal cell bodies, dendrites, unmyelinated
axons, axon terminals, and neuroglia. It appears grayish,
rather than white, because the Nissl bodies impart a gray
color and there is little or no myelin in these areas.
 White matter
 composed primarily of myelinated axons. The whitish
color of myelin gives white matter its name
Connective tissue around nerves
 Endoneurium – layer of delicate connective
tissue surrounding the axon
 Perineurium – connective tissue wrapping
surrounding a nerve fascicle
 Nerve fascicles – groups of axons bound into
bundles
 Epineurium –tough fibrous sheath surrounding a
whole nerve
Structure of a Nerve

Regeneration and Repair of Nervous Tissue
 The nervous system exhibits plasticity - the capability to change based on experience.
 sprouting of new dendrites,
 synthesis of new proteins
 changes in synaptic contacts with other neurons.
 Maturation of the nervous system continues through childhood and reflects the progressive
myelination and thickening of its axons.
 Mammalian neurons have very limited powers of regeneration, the capability to replicate or
repair damaged neurons
 In the CNS, little or no repair of damage to neurons occurs.

Even when the cell body remains intact, a severed axon
cannot be repaired or regrown. Astrocytes in CNS produce
scar tissue that prevent axon growth across damaged area
and also release chemicals that block the regrowth of axons.
 Axons and dendrites that are associated with a neurolemma

in the PNS may undergo repair if the cell body is intact,
the Schwann cells are functional, and scar tissue
formation does not occur too rapidly
 About 1-2 dys after injury to a process of a normal peripheral neuron, the Nissl
bodies break up into fine granular masses ( aa process called chromatolysis).
 By the 3-5th day, the part of the axon distal to the damaged region becomes
slightly swollen and then breaks up into fragments; the myelin sheath also
deteriorates. Macrophages phagocytize the debris. The neurolemma however
remains. The degeneration of the distal portion of the axon and myelin
sheath is called Wallerian degeneration
 Synthesis of RNA and protein accelerates and the Schwann cells on either side
of the injured site multiply by mitosis, grow toward each other, and may form a
regeneration tube across the injured area .
 The tube guides growth of a new axon from the proximal area across the injured area into the distal area previously
occupied by the original axon.
 Buds of regenerating axons begin to invade the tube formed by the Schwann cells. New axons will not grow if the
gap at the site of injury is too large or if the gap becomes filled with collagen fibers.
 Axons from the proximal area grow (1.5 mm a day) toward the distally located receptors and effectors.
Regeneration of A Nerve Axon
Motor neuron Skeletal

cell body muscle fiber
Changes Site of injury Schwann cells
over time Axon
(a)
Distal portion of
axon degenerates
(b)
Proximal end of injured axon

regenerates into tube of sheath cells
(c)
Schwann cells
degenerate
(d)
Schwann cells
proliferate
(e)
Former connection
202
reestablished
20

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Connective Tissue

 Serves as a lubricant, resists forces of compression; facilitates diffusion of

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

 Type 1-bones & tendons

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 Wandering/transient cells - lymphocytes, plasma

 Specialized cells produce the extracellular matrix

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Some connective tissues (bone, areolar connective tissue, dense irregular

Matured Connective tissue

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Specialized Connective Tissues

 Chondrocytes – mature cartilage cells that are embedded within

 Chondroclasts – associated with cartilage resorption, remove

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 Fibrocartilage has a sparse blood supply, but hyaline

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Locations - external ear/pinna, epiglottis, auditory tube and external

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Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Function - Tensile strength and ability to absorb compressive shock

Locations - Anulus fibrosus of intervertebral discs, pubic symphysis,

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

 1. Interstitial growth: mitosis of the chondrocytes

 Appositional growth: occurs peripherally, thus

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

 Hyaline cartilage is more susceptible to degenerative aging processes, eg

 Under certain conditions, crystals of calcium phosphate precipitate in the matrix of

 Note, however, that calcified cartilage is not bone.

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

 Is united to the underlying bone by

 Are osteogenic. Important in the repair of

 Very sensitive to pain cux it has one or more

 Inorganic (calcified) components (about 65% of the dry

 Osteoblasts—produce new bone matrix in a process called ossification; become

 Osteoclasts—large, motile, multinucleated cells that resorb

Compact bone Spongy bone

Perforating collagen fiber bundles

Compact bone Spongy bone

Perforating collagen fiber bundles

- Make bones lighter for easier

- In flat bones of the skull, the

 Secondary (mature or lamellar) bone

 Begins in the embryo by 2 distinct process:

NB; Bones produced by these 2 methods do not

Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings

 Bones devps. From the CT mesenchyme.