Histology

CNS

PNS

Primarily found in umbliical cord

Randomly arranged, loose and jelly-like

Primary connective tissue in the body

• Two types
•        Loose and dense CT

• Bone
• Adipose
• Bone marrow
• Cartilage

• Intercalated disks
• Uninucleated within cell

Multinucleated on periphery of cells

Changes in the relative level of physical stress cause a predictable adaptive response in all biological tissue

Very high or very low stress

• High magnitude in brief duration
• Low magnitude in long duration
• moderate magnitude with many repetitions

• Compliance
• Motivation
• Socioeconomics
• Mental status

• External support devices
• Footwear
• Ergonomic environment
• Modalities
• Gravity

• Medication
• Pathology
• Obesity
• Age
•        These all make the body less adaptable to stress

Normalized load

• Normalized deformation
• Change in length relative to original length

• Elastic region
• Plastic region
• Yield strength
• Ultimate strength
• Fracture strength
• Strain energy density

material deforms under imposition of external forces, and returns to original dimensions when unloaded

• Stiffness is the slope of the elastic region
•        Steep slope means more stiff
•        Also refered to as Young's modulus

• Material deforms under imposition of external forces and does not return to original dimensions when unloaded
•        Permanent deformation

amount of plastic strain a material can undergo before failure

Stress or strain at which plastic deformation begins

Maximum stress or strain, beyond which tissue failure occurs

Stress or strain at which tissue failure occurs

Area under stress-strain curve that represents the amount of energy absorbed by tissue before failure

• Material exhibits identical mechanical properties in all directions during loading
•        No bodily materials are isotropic

All bodily tissues are anisotropic

• Time-dependent response of a material
•        Deformation inversely related to velocity of loading
•        The faster you move, the less the tissue gives way

Load stays constant, and the shape changes

Decrease in load experienced by a material over time when deformed to a constant length

Failure of a material at a stress level lower than ultimate stress due to repeated loading cycles

• Releases vasoactive mediators such as histamine and heparin to
•        1. Increase vascular supply
•        2. Facilitate edema to dilute toxic substances
•        3. Attract in immune response

• Degrade foreign substances or injured tissues by digesting them, and sending these pieces to the cell surface which are known as antigens
• Cytokines are released to attract plasma cells

Secretes antibodies that bind to free antigen in extracellular space

Synthesizes proteoglycans and glycoproteins, and precursor molecules for collagen and elastin

Makes up most of the ECM

Resists tension, not compression

Packed into the golgie, which is then secreted into ECM

Once procollagen is seceted, an enzyme comes along to degrade the non-helical end

This forms a tropocollagen molecule, which then self aggegates and crosslinks to form a tropocollagen array

This is now collagen

• Synthesized by fibroblasts and osteoblasts
• Provides tensile strength
• Present in bone, tendon, ligaments, skin, cornea, internal organs, and dentin
• Accounts for 90% of the bodies collagen

• Synthesized by chondrocytes
• Thinner fibrils than type I
•        Found in hyaline and elastic cartilage, and intervertebral disks

• Synthesized by fibroblasts
• First collagen synthesized during wound healing, later replaced by type I
• Present in skin, loose CT in blood vessels, and internal organs

• Highly elastic recoild after stress
• Stress strain slope very flat for elastin

• Meshwork for fluid passage
• Common in bone marrow and lymphoid organs
•        Like a sponge network

• Gelatinous
• Source of viscoelasticity
• various types of glycosaminoglycans (GAGS) linkked to core protein
• Hydrophilic (resists compression)

• Cytokines indicate injury, bring in immune cells, break it down to be resynthesized
• If collagen, elastin, and other fibers overgrow, it stimulates the breakdown of the matrix

Tendon

• High collagen:elastin ratio
• Parallel collagen fiber alignment
• Transmit muscle force from bone to fascia
• Shock absorption

• Surrounds subfibrils, fibrils, and fascicles
• Minimizes shear forces during gliding of fiber bundles
• Provides pathway for blood vessels, nerves

CT capsule covering tendon

Loose sheath surrounding the whole tendon + fluid

The use of steroids degrades tendons

• 1. Connective tissue (least stiff)
• 2. Uncalcified fibrocartilage (avoids breakage)
• 3. Calcified fibrocarilage (resists shear)
• 4. Bone (most stiff)

3-5 days

• Release of vasoactive mediators by mast cells in ECM
• Phagocytosis by macrophages and other immune cells

• Primary goal is to control edema and pain
•        Most often done thru passive movement
•        RICE

day 3 up to 8 weeks

Increased collagen deposition by myofibroblast, scar tissue

Influx of fibroblasts which synthesize new fibrocartilage material --> begin as Type III to give initial structure and strength, but later changed to type I

Primary risk is adhesions, so passive ROM is very important

3 weeks - 4 months

Here, type III collagen is broken down and replaced with type I

Fibers oriented parallel to direction of stress

All activity should now be active

High collagen:elastin ration

Can increase 7% in length before failure

Has same 4 zones as cartilage

Blood clot forms between ruptured cells

Clot remodeled by fibroblasts (Type III --> Type I)

After rupture, go thru inflammatory phase

Ends of clot define borders, if close together do not need surgical intervention

• Increases of stress of 3-4% lead to hypertrophy, with increase in CSA
•        Above 4% strain, you get injury
•        The faster the strain, the faster and higher the adaptation

Found in articular cartilage of movable joints, and cartilage of the respiratory tract

Hyaline cartilage is Type II collagen

Cartilage is avascular and receives nutrients via diffsion

Purpose is to increase surface area of joint through which load is dispersed

Primarily loaded in compression

• Superficial tangential zone (20%) - collagen (resists shear)
• Middle zone (50%) resists compression (proteoglycans)
• Deep zone (30%) (resists tension)
• Calcified cartilage (anchors to bone)
• Solid matrix (20-40%) meshwork to hold proteoglycans
• Water conent (60-80%)

• A lot of elastin
• Found in external ear, epiglottis, and auditory tube
• Made of type II collagen and elastin

• Very fibrous, dense, and not highly organized
• Found in intervertebral disks, articular disks of knee, mandible, SC joint, and pubic symphysis

Made of type I collagen

Have lower proteoglycan content

Found anywhere we have disks that withstand high tensile and compressive forces

Chondrocytes live within lacuane

Chondroblasts form centers of chondrogenesis and divide by mitosis forming daughter cels within the same lacuane

Chondrogenic layer of perichondrium (outermost layer) differentiates into chondroblasts which add new layers of cells and ECM to surface of cartilage

• Swelling pressure in solid matrix created by expansion of proteoglycan solution
•        Protein backbone of proteoglycan is hyalurinon formed by GAGS, with lots of ions that repel each other, giveng them a swelling pressure that creates a cushion

• Stress within collagen matrix
• Pressure with fluid phase (first to resist load)
• Frictional drage due to fluid flow (takes energy out)

Low permability = increased stiffness = better able to withstand compressive loads

The faster you load cartilage, the less the fluid flows out

reduction of pore size, meaning less fluid flows out

No plastic deformation, has an abrupt rupture at yield point

• In healthy cartilage, collagen matrix bears only 15% of the load
•        If cartilage tears, fluid flows out and the matrix must pick up the slack, which cauess injury and healing is limited due to avascularity

• Zone 1 - Fibrin
•       First tissue laid down from blood clot
• Zone 2 - granulation tissue
• Zone 3 - fibrous tissue (initially type III then type I)
• Zone 4 - fibrocartilage
• Zone 5 - hyaline-like cartilage

• 35% of matrix
• Type I collagen (90%)
• Proteoglycans enriched in chondroitin sulfate
• Kartin sulfate
• Hyaluronic acid (primary GAGS in bones)

• 65%
• Calcium phosphage forms hydroxyapatite crystals distrubuted along length of collagen fibers

• Osteocytes reside in lacunae, which are spaces surrounded by mineralized bone
• Lacunae are conncected by canaliculi which transport nutritients
• Nutrients supplied by blood vessels in haversion canal

primary bone tissue deposited by osteoblasts derived from mesenchymal cells in embryo (flat bones)

Hyaline cartilage templates replaced by bone

• Appositional growth - bone is added between periosteum and lamellae to increase width
• Resporption/remodeling occurs at endosteal surface

• Thickness, number, and orientation of trabeculae correspond to quantitative distribution of mechanical stress
• Greatest strength is along the primary axis of lading
• Mechanical stress is a necessary stimulus for bone growth

• 1-5 days
• Local dammage to marrow and blood vessels
• Osteocyte death leads to enzymatic ECM degredation
• Platelets release cytokines/growth factors that are attracted by the hematoma
• Removal of dead bone done by osteoclasts and macrophages
• Influx of edema to clear out the damaged tissues

• 4 days to 1-4 months
• Fibroblasts and capillaries form granulation tissue to bridge gap between fragments
• Chondroblasts lay down ECM and type II collagen to form a 'soft callus'
• Osteoblasts synthesize type I collagen and regulate mineralization of matrix into hard callus of spongy bone

• 1-4 months up to 4 years
• Osteoclasts remove patches of bone from callus which are replaced by mature bone synthesized by osteoblasts
• Ossification begins at periphery where compressive forces are lowest and proceeds toward center of callus

Dense CT sheath covering entire muscle

Sheath covering muscle fascicles

Delicate sheath of reticular fibers and ECM covering each muscle

• Can be arranged in parallel, or series
• Both increases force of muscle

functional muscle unit

• connect each end of sarcomere on thin filaments
• Titin connects myosin to Z disks

During muscle contraction, the myosin pull the actin toward the center and the z disks shorten

Overlapping of thick and thin filaments

Thin filaments only

Represents the alignment of the lateral assembled tails of myosin

• Actin
• Troponin
• Tropomyosin

Double stranded helix of globular monomers

• Tn I: inhibits binding of myosin to actin
• Tn C: Binds Ca2+ to initiate contraction
• Tn T: binds tropomyosin

• Lies in actin groove
• Binds Tn T to cover myosin binding site during rest

• Myosin
• Titin

• Reversibly binds actin
• ATPase activity to break cross bridges
• 2 heavy chains form globular head with 3 binding regions
• 2 pairs of light chains

• Anchors myosin to Z disk
• Major contributor to passive elasticity of myofibril

Single motor neuron + all fibers it inervates

• Axon terminate in primary synaptic clefts containing receptors which bind ACh released from vesicles in active zones of axon terminal when depolarized
•        ACH release from cleft then binds to sarcolemma causing T-tubules to release calcium, which is the trigger for contraction

• Myosin heads bind to actin when Ca2+ is released from SR
• ATP hydrolysis causes conformational change in myosin head, pulling thin filaments past thick flaments to decrease sarcomere length
• Cross-bridge cycling continues until membrane depolarization ends and Ca2+ is pumped back into SR

• Slow ATPase activity (slow twitch)
• High SD activity (oxidative)
•        means resistant to fatigue
• Low alpha-GP activity (non-glycolytic)
• Low twitch-force and slower rise to peak

• Fast ATPase activity (fast twitch)
•        Allows for fast contraction - also more often found in thicker diameter muscle fibers
• Low SD activity (non-oxidative)
• High alpha GP activity (glycolytic)
• Highly fatigueable, and high twitch-force and faster rise to peak

• Fast ATPase activity (fast twitch)
• Intermediate SD activity (oxidative)
• Intermediate alpha-GP activity (glycolytic)
• Fatigue resistant
• Intermediate twitch-force and rise to peak

Muscle that contracts while elongating is less prone to injury because it dissipates energy while elongating

Loss of sarcomeres

Gain of sarcomeres

Coverts to type II in postural muscles

Conversion with endurance training

• Day 1-3
• Serum enzymes elevated due to fiber necrosis and sarcolemma rupture
• Phagocytosis of necrotic tissue

• Begins by day 3
• Satellite cells = source of myoblasts for muscle fiber regeneration
• Mitosis stimulated by growth factors released by macrophage
• CT regeneration by fibroblsats
• Angiogenesis

• Inflammation and pain; arthritis (use)
• Potent anticoagulant: risk bruising, bleeding, and hemorrhage
• Supressed cartilage repair and synthesis

• Organ transplants, autoimmune diseases, neoplasms
• Risk of infection, decreased bone density, myopathy, bruising, bleeding
• Peripheral neuropathies may cause weakness in intrisic muscle of hand and feat
• Delayed healing

• Glucocorticoids (cortison)
• Mineralcorticoids (aldosterone)
• Androgens (testosterone)

Increased protein and CHO metabolism; reduced immune function

Electrolyte and water metabolism

Anabolic function

• Reduced collagen synthesis, delayed wound healing, impaired epithelialization
• Anticoagulation: brusing, bleeding, hematoma
• Inhibited protein synthesis, weight loss, muscle atrophy (espeically type II), increased intramuscular CT, myopathy, focal myositis, proximal muscle weakness
• Osteoporosis/osteonecrosis due to inhibited osteoblast collagen synthesis, increased osteoclastic bone resorption
• Increased tendon strain (biceps, patellar)

Cross linking of collagen leads to stiffness

Impaired O2 delivery leads to impaired tissue healing

Impairs rate of neuron firing

Delays time to get through inflammatory phase

To build tissues, you need the substrates