Skeletal System

Spongy Bone and Compact Bone:

Spongy Bone:

• Located within the interior of a bone

• Contains a latticework structure of bone connective tissue

• Strong yet lightweight

• Appears porous

• Makes up 20% of total bone mass

Compact Bone:

• Appear solid but is in fact perforated by a number of neurovascular canals

• Formed from cylindrical structures called osteons, which display concentric rings of bone connective tissue called lamellae

• Lamellae encircle a central canal that houses blood vessels and nerves

• Makes up 80% of total bone mass

Red and Yellow Bone Marrow:

Red Bone Marrow:

• Contains reticular connective tissue, developing blood cells, and adipocytes

• Hematopoietic

• Widely distributed in children, and is located in the spongy bone of most of the bones of the body as well as the medullary cavity of long bones

• As children grow, developing blood cells decrease and adipocytes increase - yellow bone marrow

Yellow Bone Marrow:

• Fatty appearing substances commonly found in adults

Note: Adults have red bone marrow in selected portions of the axial skeleton (flat bones, vertebrae, ribs, sternum, ossa coxae), and the proximal epiphysis of each humerus and femur

Periosteum and Endosteum:

Periosteum:

• Covers the outer surface of the bone except for the areas covered by articular cartilage

• Outer fibrous layer of dense irregular connective tissue protects the bone from surrounding structures, anchors blood vessels and nerves to the surface of the bone, and serve as an attachment site for ligaments and tendons

• Inner circular layer includes the osteoprogenitor cells, osteoblasts, and osteoclasts. The osteoprogenitor cells and osteoblast produce circumferential layers of bone matrix, this is appositional growth. Anchored to the bone by numerous collagen fibers called perforating fibers

Endosteum:

• A very thin layer of connective tissue containing osteoprogenitor cells, osteoblasts, and osteoclasts

• Covers all the internal surfaces of bone within the medullary cavity

• Active during bone growth, repair, and modeling.

Cartilage Growth: bone growth and formation is dependent upon the growth of hyaline cartilage

Interstitial Growth: an increase in length that occurs within the internal regions of cartilage

Chondrocytes are stimulated to undergo rapid mitosis

Chondroblasts are formed when two cells occupy a single lacuna

Chondroblasts are pushed apart as they begin to synthesize and create a new matrix. Each cell resides in its own lacuna and turns into a chondrocyte

The cartilage continues to grow and produce more matrix

Appositional Growth: an increase in width along the periphery of cartilage

Stem cells begin to divide

Formation of undifferentiated and committed cells (turn to chondroblasts)

Chondroblasts push apart and become chondrocytes and continue to grow along the periphery.

Bone Formation (Ossification): begins in the embryo and continues as the skeleton grows during childhood and adolescence.

Intramembranous Ossification: bone formation that takes place within a membrane; formation of flat bones of the skull. It begins when mesenchyme becomes thickened and condensed with a dense supply of blood capillaries.

1. Ossification Centers form within thickened regions of mesenchyme beginning at the 8th week of development:

• Cells thickened, mesenchyme divides, committed cells differentiate into osteoprogenitor cells

• Multiple ossification centers develop and rapid mitosis of osteoblasts occurs

1. Osteoid undergoes calcification:

• Calcification entraps osteoblasts with the lacunae, these osteoblasts turn into osteocytes

1. Woven bone (immature/unorganized) and its surrounding periosteum form:

• The newly formed bone connective tissue is not well organized, this is woven bone (primary bone)

• Woven bone is replaced by lamellar bone (secondary bone)

• Mesenchyme that surrounds woven bone begins to thicken and organize to form the periosteum

1. Lamellar bone replaces woven bone, as compact and spongy bone form

• On the internal and external surfaces of bone, spaces between the trabeculae are modified and produce spongy bone

Endochondral Ossification: begins with a hyaline cartilage model and produces most bones of the skeleton

Weeks 8-12 Gestation:

1. Fetal hyaline cartilage model develops

Fetal Period:

1. Cartilage calcifies, and a periosteal bone collar forms around the diaphysis

2. Primary ossification center forms in the diaphysis

Newborn to Child:

1. Secondary ossification centers form in the epiphysis

Child:

1. Bone replaces cartilage, except the articular cartilage, and the epiphyseal plates

Late teens to adult:

1. Epiphyseal plates ossify and form epiphyseal lines

Five Zones for Growth at the Epiphyseal Plate (Interstitial Growth:

Zone of Resting Cartilage:

Near the epiphysis and farthest from medullary cavity

Small chondrocytes distributed throughout the cartilage matrix

Secures epiphysis to epiphyseal plate

Zone of Proliferating Cartilage:

Chondrocytes undergo rapid cell division

Align within their lacunae into longitudinal columns that look like a stack of coins

Columns are parallel to the diaphysis

Zone of Hypertrophic Cartilage:

Chondrocytes stop dividing

Hypertrophy of chondrocytes

Walls of lacunae become thin as chondrocytes resorb matrix when it hypertrophies

Zone of Calcified Cartilage:

Composed of two to three layers of chondrocytes

Minerals are deposited in the matrix between the columns

Calcification limits diffusion of nutrients, which results in the loss of chondrocytes

Zone of Ossification:

Formation of longitudinal channels as the walls break down between lacunae

The spaces are invaded by capillaries and osteoprogenitor cells from medullary cavity

Osteoprogenitor cells develop into osteoblasts

How a Long Bone Increases in Width (Appositional Growth):

Occur within the periosteum

Osteoblasts in the inner cellular layer of the periosteum produce and deposit bone matrix within layers parallel to the surface. This is called the external circumferential lamellae, “tree rings”

As these increase in number, the structure increases in diameter, making the bone wider

Osteoclasts along the medullary cavity resorb some bone matrix, creating an expanding medullary cavity

This continues throughout an individual’s lifetime

Effects of Hormones on Bone Growth and Remodelling:

Promote Bone Growth:

Growth Hormone: stimulates liver to produce the hormone IGF, which causes cartilage proliferation at the epiphyseal plate and resulting bone elongation

Thyroid Hormone: stimulates bone growth by stimulating metabolic rate of osteoblasts

Calcitonin: promote calcium deposition in bone and inhibits osteoclast activity

Sex Hormones: stimulate osteoblasts to promote epiphyseal plate growth and closure

Parathyroid Hormone: Increase blood calcium levels by encouraging bone resorption by osteoclasts

Calcitriol*: stimulates absorption of calcium ions from small intestine into the blood, which may cause a net decrease in calcium loss in urine

Inhibit Bone Growth:

Glucocorticoids: increase bone loss and, in kids, impair bone growth when there are chronically high levels of glucocorticoids

Serotonin: inhibits osteoprogenitor cells from differentiating into osteoblasts when there are chronically high levels of serotonin

Bone Remodeling: the constant, dynamic process of continual addition of new bone tissue (deposition) and removal of old bone tissue (resorption).

• Occur at both the periosteal and endosteal surfaces of the bone

• The relative activities of the bone cells are influenced by hormones and mechanical stress

Mechanical Stress:

• Osteoblasts increase osteoid synthesis

• Bone strength increases overtime in response

• Bony projections enlarge and become more robust

Regulating Blood Calcium Levels: essential as calcium is required for numerous physiological processes such as-

Muscle contraction

Exocytosis of molecules from cells (including neurons)

Stimulation of the heart by pacemaker cells

Blood clotting

Activation of Vitamin D to Calcitriol:

UV lights converts the precursor molecule keratinocytes in skin to vitamin D3, which is released into the bloodstream

Vitamin D3 circulates within the blood throughout the body. In the liver, vitamin D3 is converted by liver enzymes to calcidiol by adding a hydroxyl group (-OH)

Calcidiol circulates in the blood. In the kidneys, calcidiol is converted into calcitriol by adding another -OH group. Calcitriol is an active form of vitamin D3

Parathyroid Hormone and Calcitriol:

Bone: the two hormones act synergistically to increase the release of calcium from the bone into the blood increasing osteoclast activity

Kidneys: the two hormones act synergistically to stimulate the kidneys to excrete less calcium in the urine, by increasing calcium resorption in the kidney tubules

Small Intestine: like calcitriol, to increase absorption of calcium from the small intestine into the blood

Fracture Repair:

Fracture Hematoma “bruising”: A bone fracture tears blood vessels inside the bone and within the periosteum, causing bleeding. This results in a fracture hematoma that forms from clotted blood

Fibrocartilaginous (soft) callus forms:

Blood vessels infiltrate the hematoma

Hematoma is reorganized into an actively growing connective tissue called a procallus

Fibroblasts within procallus produce collagen fibers that help connect the broken ends of the bones

Chondroblasts in the connective tissue form dense regular connective tissue

Formation of the soft callus

Lasts at least three weeks

A hard (bony) callus forms:

Osteoprogenitor cells become osteoblasts and produce trabeculae of primary bone

The soft callus is replaced by the primary bone that forms a hard callus

Continue to grow for several months

Bone is remodeled:

Hard callus persists for at least 3 to 4 months as osteoclasts remove excess bony material from both exterior and interior surfaces

Compact bone replaces primary bone

Types of Fractures:

Simple: bone ends do not penetrate the skin

Compound: bone ends penetrate the superficial layer of the skin

Stress: derived from extensive exercise

Pathological: weakening of a bone due to disease

Classes of Bones:

Long Bone:

Greater in length than width

These bones have an elongated, cylindrical shaft

Ex. radius, ulna, humerus, femur, tibia, fibula.

Short Bone:

Have a length nearly equal to their width

Ex. carpals, tarsal, sesamoid bones (patella-largest)

Flat Bone:

Have a flat, thin surface that may be slightly curved

Provide extensive surface areas for muscle attachment and provide underlying soft tissues

Form the roof of the skull, the scapulae, sternum, and the ribs

Irregular Bones:

Have elaborate and sometimes complex shapes

Ex. vertebrae, hip bones, ethmoid, sphenoid, maxilla

Vitamins:

Vitamin C: increase production of collagen; aide in greater bone density

Vitamin D: play a role in calcium resorption from small intestine

Bone Functions:

Support and Protection:

• Serve as a framework for the entire body

• Protect many delicate tissues from injury or trauma

Levers for Movement:

• Serve as attachment sites for skeletal muscles (tendons)

• Muscles attached to bone contract and exert a pull on the skeleton, which function as levers

• The bones can alter the direction and magnitude of forces generated by skeletal muscles

Hematopoiesis:

• Blood cell production

• Occurs in red bone marrow connective tissue, that contain stem cells that form blood cells and platelets

Storage of Mineral and Energy Reserves:

• Calcium and phosphate are stored within and then released from bone

• When they are needed by the body, some bone connective tissue is broken down and they are released into the bloodstream

Muscular System

Tendon and Aponeurosis:

Tendon: a thick, cordlike structure composed of dense regular connective tissue

Aponeurosis: a thin, flattened sheet of dense regular connective tissue

Note: both attach a muscle either to a skeletal component (bone or ligament) or to a fascia

Connetin and Dystrophin:

Connectin: skeletal muscle fiber elasticity

• a cable-like protein that extends from the Z-discs to the M line through the core of each thick filament

• Stabilizes the position of the thick filament and maintains thick filament within a sarcomere

• Coiled and “springlike” so that during sarcomere shortening they are compressed to produce passive tension

Dystrophin:

• Part of a protein complex that anchors myofibrils that are adjacent to the sarcolemma to proteins within sarcolemma

• Extend to the connective tissue of the endomysium that encloses the muscle fiber

• Links internal myofilaments of a muscle fiber to external proteins

Connective Tissue Components:

Epimysium:

• A layer of dense irregular connective tissue that surrounds the WHOLE skeletal muscle

• Ensheaths the entire skeletal muscle for support

Perimysium:

• A layer of dense irregular connective tissue that surrounds each fascicle

• Support to each bundle of muscle fibers

Endomysium:

• Composed of areolar connective tissue that surrounds each muscle fiber

• Function to electrically insulate the muscle fibers

Muscle Fiber Types:

Fast Fibers:

• Most prevalent, largest in diameter

• Contain fast myosin ATPase but can only contract for only short bursts because ATP is provided through glycolysis

Slow Fibers:

• half the diameter of other skeletal muscle fibers

• Contain slow myosin ATPase producing slower and less powerful contractions

• Can contract over longer periods without getting fatigued as ATP is supplied through aerobic cellular respiration

Intermediate Fibers:

• Least numerous and intermediate in size

• Contain fast myosin ATPase and produces a fast and powerful contraction with ATP provided primarily through aerobic cellular respiration

• Delivery of nutrients and oxygen is lower as it has a less extensive capillary network

Oxidative and Glycolytic Fibers:

Oxidative Fibers:

• Specialize in providing ATP through aerobic cellular respiration

• Extensive capillary network

• Large numbers of mitochondria and myoglobin

• Fatigue-resistant

Glycolytic Fibers:

• Specialize in providing ATP through glycolysis

• Less extensive capillary network

• Fewer mitochondria and myoglobin

• Fatigable

Skeletal Muscle Contraction: The anatomic structures and associated physiological processes of skeletal muscle contraction include the events that occur at the neuromuscular junction, sarcolemma, T-tubules, sarcoplasmic reticulum, and sarcomeres

1. Neuromuscular Junction, Excitation of a Skeletal Muscle Fiber: Release of neurotransmitter ACh from synaptic vesicle excites the skeletal muscle fiber

2. Sarcolemma, T-tubules, and Sarcoplasmic Reticulum, Excitation-contraction Coupling: ACh binding triggers propagation of an action potential along the sarcolemma and T-tubules to the sarcoplasmic reticulum, which is stimulated to release calcium

3. Sarcomere, Crossbridge Cycling: Sarcomeres shorten and the skeletal muscle fiber contracts

Muscle Twitch:

A single, brief contraction period and then relaxation period of a skeletal muscle in response to a single stimulation

Subthreshold Stimulus: minimum voltage needed to stimulate the skeletal muscle to generate a muscle twitch

Latent Period:

• Occurs after a stimulus is applied and before the contraction

• The time elapsed between stimulation of the muscle fiber and the generation of a contractile force

Contraction Period:

• Repetitive powerstrokes pull the thin filaments past the thick filaments, shortening sarcomeres

• Tension increases

Relaxation Period:

• Release of crossbridges as calcium is returned to the sarcoplasmic reticulum

• Tension decreases

• Depends upon elasticity of connectin

Wave Summation:

Occurs in skeletal muscle during repetitive stimulation. Happens after an action potential arrives at the muscle fiber before the relaxation phase of muscle contraction is complete

Incomplete tetany:

• In this scenario, the muscle fiber has partially relaxed before the arrival of the next stimulus.

• The individual twitches or contractions can be observed separately, and there is a partial relaxation between them.

• This allows the muscle to partially recover and prevents sustained contraction

Tetany:

• If the frequency of stimulation is high enough, the muscle does not have time to relax between stimuli.

• The individual twitches fuse into a sustained contraction, and the muscle does not return to its resting state.

• This type of contraction is more forceful and sustained compared to incomplete tetanus.

Skeletal Muscle Relaxation:

1. Termination of rapid nerve signals propagated along motor neuron, when it stops ACh is no longer released

2. ACh is hydrolyzed by acetylcholinesterase

3. ACh receptors close, end-plate potentials at the motor end plate and the action potentials along the sarcolemma and T-tubules cease

4. Calcium channels return to their original position

5. Calcium is returned to the terminal cisternae by pumps and returned to its storage within sarcoplasmic reticulum

6. Troponin returns to its original shape when calcium is removed, with tropomyosin being simultaneously moved over to myosin binding sites on actin - prevents crossbridge formation

7. Muscle returns to its original position from the release of tension in connectin (springs)

Notes*:

• Calcium levels within the cytosol must be kept low to prevent calcium from binding with phosphate ions

• This would result in the formation of hydroxyapatite, which calcify and harden muscles

• A significant amount of ATP is used by the pumps of the SR and required for contraction and relaxation

Parts of a neuromuscular junction: Excitation of a Skeletal Muscle Fiber. The first physiologic event of skeletal muscle contraction.

Calcium Entry at Synaptic Knob:

A nerve signal is sent along a motor neuron

The nerve signal triggers the opening of voltage-gated calcium channels within the synaptic knob and calcium moves down its gradient

Release of ACh from Synaptic Knob:

The binding of calcium to synaptic vesicles triggers the merging of synaptic vesicles with the synaptic knob

Exocytosis of ACh into synaptic cleft

Binding of ACh at Motor End Plate:

ACh diffuses across the fluid-filled synaptic cleft to bind with ACh receptors within the motor membrane - causes excitation

Excitation-Contraction Coupling*: The second physiologic event of skeletal muscle contraction involving the sarcolemma, T-tubules, and sarcoplasmic reticulum.

Development of an End-Plate Potential at the Motor End Plate:

The opening of ACh receptors/channels allow relatively small amounts of sodium to rapidly diffuse into the skeletal muscle fiber

Potassium diffuses out

These changes in membrane potential are short-lived and local

If there is a sufficient gain of positive charge to depolarize the RMP, and end-plate potential is produced, causing an action potential

Initiation and Propagation of Action Potential Along the Sarcolemma and T-tubules:

EPP triggers an action potential that is propagated along the sarcolemma and T-tubules

Voltage-gated sodium channels open - depolarization

Voltage-gated potassium channels open - repolarization, that reestablishes the RMP

Release of Calcium from the Sarcoplasmic Reticulum:

When the action potential reaches a triad it:

i. Stimulates a shape change to voltage-sensitive calcium channels within the T-tubule membrane

ii. Causes a shape change in calcium release channels, causing them to open

This allows calcium to diffuse out of the terminal cisternae of the SR into the cytosol

Calcium now “mingles” with the thick filaments and thin filaments of myofibrils

Crossbridge Cycling*: The third physiologic event in contraction that involves binding of calcium and cross bridge cycling.

Calcium Binding:

Calcium released from SR binds to a subunit of globular troponin (component of thin filaments; this changes the shape of troponin

RECALL: troponin-tropomyosin complex

When troponin changes shape, the entire complex is moved and the myosin binding sites of actin are exposed

(2-5) - Crossbridge Cycling: repeated

Crossbridge Formation:

Myosin heads attach to exposed myosin binding sites of actin

Formation of a crossbridge within thick (myosin) and thin (actin) filaments

Power stroke:

After forming a crossbridge, the myosin head swivels

This causes the thin filaments to pull a small distance past the the thick filament toward center of the sarcomere

ADP and P₁ are released and ATP binding sites are available again

Release of Myosin Head:

ATP binds to ATP binding site of a myosin head

Release of myosin head from binding site of actin

Resetting of Myosin Head:

Myosin ATPase splits ATP into ADP and P₁ providing the energy to reset myosin head

Role of Calcium Ions & ATP in Muscle Contraction:

Muscle contractions are controlled by the actions of calcium, released from signals of the nervous system to contact

When calcium ion levels are high enough and ATP is present, calcium ions bind to the troponin which displaces tropomyosin, exposing the myosin binding sites on actin

This allows myosin to attach to a binding site on actin forming a crossbridge

Trigger a muscle contraction

Function of Creatine Phosphate:

What is it: A molecule with high energy chemical bonds between creatine and P_i, and is present in tissues with both large and fluctuating energy needs (muscle and brain

During active contraction, the Pi in creatine phosphate is readily transferred to ADP to form additional ATP and creatine, an enzymatic reaction catalyzed by creatine kinase

This provides an additional 10 to 15 seconds of energy during maximum exertion

In summary, creatine phosphate helps maintain a constant concentration of ATP in muscle during sudden bursts of activity that would deplete ATP concentration in the cell

Function of Myoglobin:

It binds oxygen when the muscle is at rest and releases it for use during muscular contraction

The additional source of oxygen provides the means to enhance aerobic cellular respiration and the production of ATP

Muscle Fatigue: the reduced ability of the skeletal muscle to produce muscle tension. One cause is during excessive exercise (marathon) where glycogen stores are depleted

Physiologic Events:

Excitation at the Neuromuscular Junction:

Caused by insufficient free calcium at the NMJ to enter the synaptic knob or by a decreased number of synaptic vesicles to release ACh

This limits the ability of a somatic motor neuron to stimulate a skeletal muscle

Excitation-Contraction Coupling:

Muscle fatigue may be due to a change in sodium and potassium concentration

Inhibits an action potential along the sarcolemma

Cross Bridge Cycling:

Increased phosphate ion concentration, which interferes with the release of the myosin head during crossbridge cycling

Lower calcium levels results in less calcium binding to troponin, reducing cross bridge formation - weaker muscle contraction

Note: A lack of ATP is NOT a cause of muscle fatigue, as ATP levels are maintained through aerobic cellular respiration during sustained exercise

Functional Categories of Smooth Muscle:

Multi Unit:

• Found within the eye in both the iris and ciliary muscles, arrector pili muscles in the skin, the wall or larger air passageways within the respiratory system

• Arranged into motor units

• Have a neuromuscular junction

• Stimulated to contract independently

Single Unit:

• Within walls of digestive, urinary and reproductive tracts, etc

• Functionally linked by gap junctions between cells

• Stimulated to contract as a group

Smooth Muscle Contraction and Relaxation: resembles skeletal muscle contraction as it is initiated by calcium, the sliding of thin filaments past thick filaments, and requires ATP.

Contraction:

Opening of voltage-gated calcium channels:

An action potential triggers the opening of voltage gated calcium channels

Calcium enters the sarcoplasm, from interstitial fluid

Binding of calcium to calmodulin (protein):

Formation of a calcium-calmodulin complex

Activation of myosin light-chain kinase (MLCK):

Calcium-calmodulin complex activates MLCK, a phosphorylating enzyme

Activation of myosin head:

Activated MLCK phosphorylates (adds phosphate to) myosin head

This activates myosin

Crossbridge formation, power stroke, reattachment:

Activated myosin heads bind to thin filaments to form crossbridges.

Myosin ATPase hydrolyzes ATP, providing the energy for the powerstroke

This is repeated

The force generated is transferred to the anchoring filaments, and the smooth muscle shortens.

Relaxation: more complex than contraction

In addition to requiring both cessation of stimulation and the removal of calcium from the sarcoplasm, relaxation also requires the dephosphorylation of myosin by myosin light-chain phosphatase

Articulations:

Structural Classifications of Joints:

1. Fibrous

2. Cartilaginous

3. Synovial

Fibrous Joints:

1. Gomphosis:

• Periodontal membranes that hold a tooth to bony jaw (synarthrosis=immovable)

1. Suture:

• Connects skull bones (synarthrosis=immovable)

1. Syndesmosis:

• Interosseous membranes between bones (amphiarthrosis=slightly movable)

Cartilaginous Joints:

1. Synchondrosis:

• Contain hyaline cartilage (synarthrosis)

1. Symphysis:

• Contain fibrocartilage (amphiarthrosis)

Synovial Joints: all diarthroses (mobile)

Movements: uniaxial, biaxial, multiaxial

Recall from Lab: plane, hinge, pivot, condylar, saddle, ball-and-socket

Types of Levers in the Body: three classes of levers are found in the human body:

First Class Levers:

• Fulcrum in the middle between the effort (force) and resistance

• “Scissors”- the effort is applied to the handle of the scissors while the resistance is at the cutting end of the scissors

• The fulcrum (pivot for movement) is along the middle of the scissors, between the handle and the cutting ends

In the body:

• atlanto-occipital joint of the neck

• Effort: posterior neck muscles pull inferiorly on the nuchal lines of the skull and oppose the tendency of the head

• Resistance: the head is opposed by the effort to tip anteriorly

Second Class Levers:

• Resistance in the middle between the fulcrum and the applied effort

• “Lifting the handles of a wheelbarrow”- allows it to pivot on its wheel at the opposite end and lift a load (resistance) in the middle, the lifting motion is the effort.

• A small force can balance a larger weight in this type of lever, because the effort is always farther from the fulcrum than the resistance.

In the body:

• Plantar-flexion of the foot (“tippy-toes”)

• The contraction of the calf muscle (gastrocnemius) causes a pull superiorly by the calcaneal tendon attached to the heel (calcaneus)

Third-Class Levers:

• Effort in the middle between resistance and fulcrum

• “Picking up a small object with a pair of forceps”

In the body:

• Elbow: fulcrum is the joint between humerus and ulna, effort is applied by the biceps brachii muscle at its attachment to the radius, and the resistance is provided by any weight in the hand or by the weight of the forearm itself

• Mandible: fulcrum is the temporomandibular joint, effort is the temporalis muscle, resistance is the food being bitten