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Integument
-skin
-cutaneous membrane
Integumentary system
Skin
– Accessory Structures (Epidermal Derivatives)
(Nails, hair, sweat glands, sebaceous glandsus glands)
epidermis
-epithelium
-4-5 distinct layers/strata
dermis
-connective tissue
-2 distinct layers
Hypodermis/Subcutaneous
Layer
-Adipose and areolar
connective
-Not part of the integumentary
system
Epidermis
Keratinized stratified squamous
epithelium
• Avascular
• Composed primarily of
keratinocytes
• Five layers (strata):
– Stratum basale
– Stratum spinosum
– Stratum granulosum
– Stratum lucidum*
• Only in thick skin
– Stratum corneum
• Deep 3 layers are living
keratinocytes
• Superficial 2 layers are dead
keratinocytes
Epidermis
Keratinocytes
• Epidermal cells
• Manufacture and store
keratin protein
• Keratin:
– Intracellular fibrous protein
– Hard and water-resistant
• Structure changes as they
migrate to more superficial
layers
Stratum Basale
• Deepest layer – adhered to
basement membrane
• Mitotic cells
• Single layer of cuboidal or
columnar cells
• Cell types:
– Keratinocytes (most abundant)
• Basal stem cells
• Divide to regenerate epidermis
– Melanocytes
• Produce and store melanin
pigment
• Shield DNA from UV radiation
– Tactile (Merkel) cells
• Receptor that stimulates nerve
endings
• Sensitive to touch
Stratum Spinosum
Second-deepest layer
• 8-10 layers of “spiny”
keratinocytes
• Amitotic:
– New cells from stratum basale
push into this layer
• Keratin synthesis begins here
• Some dendritic (Langerhans) cells
– Immune cells
– Macrophages (phagocytize)
• Desmosomes – cells attached to
each other
Stratum Granulosum
Middle layer of epidermis
• “Granular layer”
• 3-5 layers of flatter cells
• Amitotic
• Keratinization process begins
– Lots of keratin (granules)
synthesis
– Membrane thickening and cell
flattening
– Nucleus and organelles
disintegrate
– Cells die
Stratum Lucidum
Only found in thick
skin (palms and
soles)
• Translucent/clear
• 2-3 layers of
flattened, dead
keratinocytes
Stratum Corneum
Outermost layer of epidermis
• Thickest layer: 15-30 cells
• Composed entirely of dead,
interlocking keratinized cells
– No nuclei
• Protective against abrasion,
microbe penetration, and deeper
tissue dehydration
• Two weeks to arrive at stratum
corneum
• Stays in stratum corneum for ~2
weeks before sloughing off
• Entire layer replaced in ~4 weeks
Thick skin
Palms of hands and soles of feet
– Contains sweat glands
– No hair follicles or sebaceous glands
– Contains all 5 epidermal strata
– 0.4 – 0.6 mm of epidermis
Thin skin
– Remainder of the body
– Contains hair follicles, sebaceous glands,
sweat glands
– No stratum lucidum – only 4 strata total
– 0.075 – 0.15 mm of epidermis
Skin Color: Melanin
Pigment produced by melanocytes
• Melanin transferred to
keratinocytes
• Protects DNA from UV rays
• Black/brown/tan/yellow pigment
– Eumelanin: brown and black
shades
– Pheomelanin: tan, yellow, and red
shades
• Same number of melanocytes
– Different activity of melanocytes
– Different type of melanin
produced
• Amount of melanin influenced by
heredity and UV exposure
– Increased UV light stimulates
melanocytes
Hemoglobin
– O2-binding protein in erythrocytes
– Becomes brighter red upon binding with
oxygen
Carotene
– Yellow-orange pigment
– In certain vegetables
– Accumulate in keratinocytes
Dermis
• Immediately deep to the epidermis
• Strong and flexible
• Highly vascularized
• Many nerve endings
• Dendritic cells – motile immune cells
• Protein fibers:
– Primarily collagen fibers
– Contains some elastic and reticular
fibers
• Composed of two layers of connective
tissue proper
– Papillary layer
– Reticular layer
Papillary Layer of Dermis
• Superficial layer of the dermis
• Areolar connective tissue
• Contains dermal papillae – projections into epidermis
– Contact epidermal ridges
– Blood vessels – capillaries
– Sensory nerve endings
Dermal Papilla
Epidermal Ridge
Reticular Layer of Dermis
• Deep layer of the dermis
• Extends to subcutaneous layer/hypodermis
• Dense irregular connective tissue
– Collagen fiber network
• Other structure:
– Hair follicles, sebaceous glands, sweat glands, nerves, blood vessels
Cleavage Lines and Stretch Marks
• Most CT fibers of the dermis are
oriented in parallel bundles
• Lines of cleavage:
– Tension lines
– Predominant orientation of
collagen fiber bundles
• Collagen fibers = resist stretch,
impart tensile strength
• Elastic fibers = allow stretch and
recoil
• Stretch marks (striae) = tearing
of collagen fibers
Subcutaneous Layer
• Hypodermis or superficial fascia
• Deep to integument
• Composition:
– Areolar connective tissue
– Adipose connective tissue
– Highly vascular
• Functions:
– Protection
– Energy reservoir
– Thermal insulation
Nails
• Scalelike modification
of stratum corneum
• Forms of dorsal edges
of fingers and toes
• Function: protection
• Structure:
– Free edge
– Nail body
– Nail root
Hair
• Slender filament of fused, dead
keratinized cells
• Found everywhere except palms, soles,
and parts of external genitalia
• 3 Types:
– Lanugo
• Fetal hair (third trimester)
• Fine, unpigmented, downy hair
– Vellus
• Primary human hair
• Found on limbs
• Fine, lightly pigmented
– Terminal Hair
• Coarser, pigmented, long hair
• Scalp, eyebrows, eyelashes, testosterone-
influenced beards, axillary and pubic regions
at puberty
Hair Structure
Slender filament of fused
keratinized cells
• Three zones:
– Hair bulb:
• Epithelial cells surrounding hair
papilla
• Papilla: CT surrounding
neurovasculature
• Region of living cells
– Root:
• Area from bulb to skin surface
• Composed of dead, keratinized
cells
– Shaft:
• Area that extends beyond skin
surface
• Composed of dead, keratinized
cells
Hair Structure: Matrix
– Area of hair production at base of hair bulb
– Epithelial cell division
Hair Shaft
– Medulla
• Central core of hair, remnant of matrix
• Flexible, soft keratin
– Cortex
• Flattened cells closer to outer hair surface
• Relatively hard
– Cuticle
• Layer of single cells coating hair around cortex
Follicle
– Oblique tube surrounding hair root
– Extends into dermis/subcutaneous layer
– Outer CT root sheath originates from dermis
– Inner epithelial tissue root sheath originates from
epidermis
Arrector pili
– Smooth muscle ribbon
– Extend from hair follicle to dermal papillae
Hair Growth and Replacement
Three stages of hair growth
• Anagen: active phase
– 2-7 years
• Catagen: regression/transition phase
– 2-3 weeks
• Telogen: resting/shedding phase
– 2-4 months
Exocrine Glands: Sweat Glands
Sweat glands = sudoriferous
glands
• Coiled, tubular secretory
portion in reticular dermis
• Contain duct and pore
• Function: thermoregulation
• Excretion by exocytosis
– Both classified as MEROCRINE
(physiological classification)
• Two types:
– Eccrine/Merocrine
– Apocrine
Eccrine/Merocrine
– Dermal sweat glands
– Most numerous, widely distributed
– Secrete sweat (99% water, 1% electrolytes,
waste)
– Function: thermoregulation
Apocrine
– Larger and usually deeper in
dermis/hypodermis
– Viscous and cloudy secretion containing
lipids and proteins
– Produce distinct odor when acted upon by
bacteria
– Discharge secretions into hair follicles at
axilla, around nipples, pubic, and anal
region
– Produce secretions starting at puberty
Sebaceous Glands
• Holocrine glands
• Activated by sex
hormones
• Produce sebum
– Oily and waxy secretion
• Functions:
– Bactericidal
– Lubricates and
waterproofs skin and hair
Regeneration
– Replacement of damaged or dead cells via cell division
– Replacement with same cell type
– Ultimately restores tissue function
Fibrosis
– Process of scar tissue deposition in connective tissue
• Primarily collagen fibers produced by fibroblasts
– Occurs when extensive damage or cells unable to
divide
– Functional activities not restored
Stages of wound healing
1. Damaged vessels
release blood into
wound
2. Blood clot forms and
leukocytes clean
wound
3. Blood vessels grow and
granulation tissue
forms
4. Epithelium regenerates
and connective tissue
fibrosis occurs
Embryology
• Epidermis – derived
from ectoderm
• Dermis – derived from
mesoderm
Aging
Skin repair takes longer –
decreased stem cell activity
• Thinner skin
• Decreased collagen fibers
• Decreased elasticity of elastic
fibers
• Epidermal dendritic cells
decrease in number and
efficiency – decreased immune
function
• Hair follicles reduce melanin
production (grey) or
completely stop melanin
production (white)
Bone (osseous tissue)
– Compact: dense, rigid, solid bone
– Spongy: trabecular, porous bone
Cartilage
– Hyaline:
• Costal cartilage
• Articular cartilage
• Epiphyseal plates
• Fetal skeleton
– Fibrocartilage:
• Weight-bearing cartilage
Dense Regular Connective Tissue
– Ligaments: anchor bone to bone
– Tendons: anchor muscle to bone
Axial skeleton
– Skull
– Vertebral column
– Rib cage
Appendicular skeleton
– Bones of limbs
– Pectoral girdle (scapula and clavicle)
– Pelvic girdle
Long Bones
• Greater in length
than width
• Most common bone
shape
Short bones
• “Cube” – mostly
equivalent length and
width
• Examples:
– Carpals (wrist)
– Tarsals (ankle)
Sesamoid bone
Develop within tendon
• Patella: largest sesamoid
bone
Flat Bones
• Flat, thin, sometimes curved
• Examples:
– Sternum
– Scapulae
– Ribs
– Most of skull
• Functions:
– Protection of underlying soft
tissue
– Muscle attachment
Irregular bones
• Irregular or elaborate shape
• Cannot be classified as
long, short, or flat bones
• Examples:
– Ossa coxae
– Vertebrae
– Ethmoid
– Sphenoid
– Maxilla
Long Bones: Structure
• Articular Cartilage
– Hyaline Cartilage
• Epiphysis
– Proximal
– Distal
• Metaphysis
– Epiphyseal Plate/Line
• Diaphysis
– Medullary Cavity
• Nutrient Foramen
– Entry/exit neurovasculature
Epiphysis
• Expanded end
• Both proximal and distal epiphyses
• Compact bone surrounding spongy
• Covered by articular cartilage
– Hyaline cartilage
– Function: reduce friction and absorb shock
Metaphysis
• Between epiphyses and diaphysis
• Contains epiphyseal plate (growing
bone) or epiphyseal line (remnant)
Diaphysis
• Shaft region
• Mostly compact bone
• Medullary (marrow) cavity:
– Filled with bone marrow
• Red: children
• Yellow: adults
– Can extend into spongy bone
(adult)
– Lined with endosteum
Periosteum
– Covers outer surface (except areas with
articular cartilage)
– Two layers:
• Fibrous (outer): dense irregular connective
tissue
• Cellular (inner): contains cells (osteoprogenitor
cells, osteoblasts, and osteoclasts)
– Perforating (Sharpey’s) fibers: collagen
fibers anchoring periosteum to bone
Endosteum
– Covers inner surface, i.e. medullary cavity
– Thin connective tissue containing cells
External Surface
– Periosteum
– Compact Bone
Internal Surface
– Spongy Bone
– No medullary cavity
• No endosteum
Red Bone Marrow (myeloid tissue)
• Hematopoietic: forms blood cells
• Composition:
– Reticular connective tissue
– Developing blood cells
– Adipocytes
• Location:
– Adults:
• Proximal epiphyses of humerus and femur
• Spongy bone of some axial flat bones (skull, ribs,
sternum, etc.)
– Children:
• Most spongy bone
• Medullary cavity of long bones
Yellow Bone Marrow
During maturation composition of
most red marrow changes
– Increase in adipocytes
– Decrease in developing blood cells
• Location:
– Adults:
• Medullary cavities
• Most epiphyses
– Children:
• Low distribution
Osteogenic (Osteoprogenitor) cells
– Mesenchyme-derived stem cells
– Located in periosteum and endosteum
Osteoblasts
– Formed from osteogenic cells
– Synthesize and secrete bone matrix (osteoid)
– Become trapped in matrix once osteoid calcifies
Osteocytes
– Mature bone cells
– Connect to other osteocytes via projections
– Maintain bone matrix
Osteoclasts
– Multinucleate, phagocytic cells
– Break down bone (resorption) to release
minerals (ex. Ca2+)
Osteoid (organic)
– Produced by osteoblasts
– Collagen fibers
– Semisolid ground substance containing
proteoglycans
• Responsible for resistance to
stretching and twisting
Inorganic Component
Calcium salts (calcium phosphate,
calcium hydroxide)
• Responsible for rigidity and hardness
of bone tissue
Osteon
structural and functional unit of bone
– Cylindrical structure parallel to bone diaphysis
Central (Haversian) Canal:
– Center channel of osteon
– Contains neurovasculature
Lamellae
– Concentric rings of bone tissue
– “Growth Rings'‘
Perforating (Volkmann) Canals
– Perpendicular to osteon/central canal
– Connect neurovasculature from periosteum and
between osteons
Lacunae
– Spaces housing osteocytes
Canaliculi
Channels connecting lacunae
Spongy Bone
• Trabeculae
– Lattice of narrow rods/plates of bone tissue
• No osteons
• Lamellar patterns within plates
• Contains red bone marrow
Cartilage
• Semirigid connective tissue
• Avascular
• No nerve supply
• Extracellular Matrix:
– High water content
– Like bone, but lacking calcium
salts (more flexible and
compressible)
• Two kinds in skeletal system:
– Hyaline Cartilage
– Fibrocartilage
Hyaline Cartilage
Structure:
– Cells: chondrocytes in lacunae
– Matrix: collagen and elastin
• Function:
– Bone attachment
– Covering epiphyses
– Growth (in growth plate)
– Model for fetal skeleton
development
• Location:
– Articular cartilage (joints)
– Costal cartilage (attach ribs to
sternum)
– Epiphyseal plates
– Nasal cartilage
Fibrocartilage
• Structure:
– Cells: chondrocytes in lacunae
– Matrix: mostly collagen
• Function:
– Weight bearing (withstands
compression)
• Location:
– Intervertebral discs
– Pubic symphysis
– Cartilage pads of knee joints
(menisci)
Perichondrium
• Structure:
– Dense irregular connective tissue
– Vascular
– Innervated
• Surrounds hyaline cartilage (except articular cartilage)
• Supplies nutrients and oxygen to hyaline cartilage
Cartilage Growth
• Cells:
– Chondrocytes: mature cartilage
cells
– Chondroblasts: mitotic cartilage
cells
• Two types of growth
– Appositional:
• Increase in width along outer
edge/periphery
• Perichondrium-dependent
– Interstitial:
• Increase in length
• Growth from within internal
regions of cartilag
Intramembranous Ossification
• Forms within thickened areas of
mesenchyme with dense vascularization
– Mesenchyme cells → osteoprogenitor cells →
osteoblasts
• Osteoblasts produce osteoid
• Osteoid is calcified
• Forms compact bone outside and spongy bone
inside
– Mesenchyme cells → periosteum
• Occurs ~W8 of development
• Produces flat bones of skull and face,
mandible, clavicle
• Replaces fontanels
Endochondral Ossification
Produces most bones
– Upper and lower limbs, pelvis, vertebrae, ends of clavicle
• Forms within hyaline cartilage model
– Fetal hyaline cartilage model develops
– Cartilage calcifies and periosteal bone collar forms around diaphysis
– Chondrocytes die and osteoblasts develop within calcified cartilage
– Osteoblasts form primary ossification center (at center of diaphysis)
• Osteoid production extends towards both epiphyses along cartilage template
– Secondary ossification centers form in the epiphyses (in some cases, secondary
ossification continues after birth)
• Production of osteoid to extend bone tissue
– Osteoclasts resorb some bone matrix at center of diaphysis to form medullary cavity
• Bone replaces almost all cartilage except articular cartilage and epiphyseal
cartilage
Interstitial Bone Growth
• Increase in bone length
• Bone growth within the
epiphyseal plate
• Begins during embryologic
development and continues
through puberty
• Five distinct zones:
– Reserve (Resting) Zone
– Proliferative Zone
– Hypertrophic Zone
– Calcified Matrix Zone
– Ossification Zone
Reserve Zone: (nearest epiphysis)
– Secures epiphysis to epiphyseal plate
– Mature and healthy hyaline cartilage
Proliferative Zone
Mitotic chondrocytes make more cartilage
Hypertrophic Zone
– Chondrocytes stop dividing, but increase in
size
Calcified Matrix Zone
– Calcification of matrix and death of
chondrocytes
Ossification Zone: (nearest diaphysis)
– Invasion of capillaries (nutrients) and
osteoprogenitor cells (bone formation)
– Osteoprogenitors differentiate into
osteoblasts which produce osteoid within
remaining calcified cartilage matrix
Appositional Bone Growth
• Increase in bone width/circumference
• Bone growth within the periosteum
• Osteoblasts in periosteum continue to lay down bone
– External circumferential lamellae
• Osteoclasts in endosteum simultaneously breaking down bone
within medullary cavity
Bone Remodeling
• Dynamic and continual process:
– Resorption: removal of old bone tissue
– Deposition: addition of new bone tissue
• Two stimuli for remodeling:
– Mechanical stress:
• Stress applied to bone
• Detected by osteocytes → signal
osteoblasts to produce matrix
• Calcification occurs
• Areas of greater stress develop greater
density
– Attachment sites for muscles
– Weight bearing
– Exercise
– Hormonal influence
Hormonal Control: Increase Growth
• Growth hormone (GH)
– Directly and indirectly stimulates growth at epiphyseal plate
• Thyroid hormone (TH)
– Works with GH at epiphyseal plate
– Stimulates osteoblast activity
• Sex hormones (testosterone, estrogen)
– Stimulates aggressive bone growth in area of epiphyseal plate
– Stimulates osteoblast activity
• Calcitonin*
– Inhibits osteoclast activity – inhibits resorption
Hormonal Control: Decrease/Inhibit Growth
• Parathyroid Hormones:
– Encourage osteoclast resorption activity
• Glucocorticoids:
– Impair bone growth and increase bone loss
• Serotonin:
– Chronically high levels inhibit osteoprogenitor
differentiation (decrease levels of osteoblasts)
Regulation of Blood Calcium
• Calcium homeostasis requires precise control over
calcium uptake, loss, and storage
• Bones represent a huge store of calcium
• Blood calcium levels regulated by hormones:
– Calcitriol:
• Stimulates absorption of Ca2+ from small intestine into blood
• Stimulates osteoclast activity → release of Ca2+ from bones into blood
– Parathyroid Hormone:
• Stimulates osteoclast activity → release of Ca2+ from bones into blood
– Calcitonin:
• Inhibits osteoclast activity
• Leads to reduction in blood calcium levels
Effects of Aging
• Decrease in tensile strength
– Decreased rate of protein synthesis by
osteoblasts
• Demineralization: loss of calcium and
other minerals
– Osteopenia: insufficient ossification
causing thinning and weakening of bone
– Osteoporosis: reduction in bone mass
that compromises normal functioning
• Decrease in bone mass
– Due to loss/dysregulation of hormones
(GH, sex hormones)
Fracture Repair
1. Formation of fracture hematoma
2. Formation of fibrocartilaginous (soft) callus
3. Formation of bony (hard) callus
4. Bone remodeling
Articulations
• Articulation = joint
• Place of contact between
bones, bones and
cartilage, or bones and
teeth
• Classification by
– Function
• Extent of movement
– Structure
• Presence/absence of joint
cavity
• Type of connective tissue
Fibrous Joints
• No joint cavity
• Held together by dense
regular CT
• Either synarthroses or
amphiarthroses
• Three types:
– Gomphoses
– Sutures
– Syndesmoses
Fibrous Joints: Gomphoses
Gomphosis = peg in
socket
• Only found between
tooth (peg) in alveolar
process (socket)
• Tooth held in place by
fibrous membrane
– Periodontal membrane
• Synarthrosis (immobile)
Fibrous Joints: Sutures
• Suture = “seam”
• Interlocking irregular
edges
• Only found between
certain bones of the skull
• Sutures → synostoses
– Obliterated suture
– Due to fusion of bone
across suture line
(ossification) over time
• Synarthroses (immobile)
Fibrous Joints: Syndesmoses
• Parallel bones held only
by long strands of
dense regular CT
• Interosseous
membrane between
bones
– Radius – ulna
– Tibia – fibula
• Amphiarthrosis (slight
mobility)
Cartilaginous Joints
• No joint cavity
• Cartilage between
bones
– Hyaline or fibrocartilage
• Either synarthrosis or
amphiarthrosis
• Two types:
– Synchondroses
– Symphyses
Cartilaginous Joints: Synchondroses
• Contain hyaline cartilage
• Synarthroses (immobile)
• Locations:
– Epiphyseal plates
– Costochondral joints (rib –
costal cartilage)
– First sternocostal joints
• Can be temporary –
become synostoses
Cartilaginous Joints: Symphyses
Contain fibrocartilage
• Resist compression and
tension; shock
absorption
• Amphiarthroses (slight
mobility)
• Locations:
– Pubic symphysis
– Intervertebral joints