Download ANATOMY and PHYSIOLOGY block II

Skeletal System
The skeletal system is composed of bone, cartilage and connective tissues. The skeletal system's most
conspicuous functions are protection, support, and, combined with the muscular system, movement. Less
obvious but equally important are its roles in blood cell production and calcium storage.
The following topics will be covered in this category.
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Skeletal Structure and Histology
Bone Development
Tooth Formation
Calcium Metabolism
Articulations and Movement
Skeletal Structure and Histology
Skeletal System
Primary functions
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Movement - acts as lever system, directs forces generated by muscles across joints
Support - weight (load) bearing, framework for soft tissue attachment
Protection - surrounds vital organs, provides low friction surfaces
Storage- Ca+2 & PO4, reserve lipid in yellow marrow
Blood cell production - RBC, WBC & platelets produced in red marrow
What are the requirements of a system that is capable of the above functions?
Cartilage Tissue
Characteristics
Stiff/rigid but still flexible/elastic/resilient, not particularly strong, avascular
Functions
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Protection - areas of reduced friction at joints
Support - fetal skeleton preformed in cartilage, support for some soft tissues
Tissue Components (compact connective tissue)
1. Chondrocytes - oval cells occur singly or in groups
a. located in small spaces called lacunae surrounded by matrix
b. dependent on diffusion for nutrients and gases
2. Matrix - firm gel-like ground substance with network of fibers
a. proteoglycans containing chondroitin sulfate
i.
proteoglycans trap water (~75%) to produce stiffness, compression slowly forces
water out and deforms cartilage, at load release there is a rapid elastic recovery
and slower rehydration
b. type and amount of fibers determines mechanical properties, collagen fibers provide
strength
c. mostly avascular, secretes antiangiogenesis factor
3. Perichondrium - outer dense fibrous C.T. layer + inner layer of chondroblasts*
Growth and Replacement
1. Interstitial growth - occurs within the matrix
a. chondrocytes divide and secrete new matrix
b. occurs in embryonic tissues
2. Appositional growth - adds new layers on outside
a. chondroblasts* divide and secrete new matrix
b. occurs throughout adolescence but little in adult
3. In adults cartilage seldom grows and heals slowly
Types of cartilage
Distinguished on basis of the amount of matrix and the fiber type present
1. Elastic - very flexible
a. irregularly arranged branching elastic fibers for increased flexibility
b. scattered cells in lacunae with less matrix, which maintains shape
c. ex. external ear, auditory tube, epiglottis, some laryngeal cartilages
2. Hyaline - stiff but flexible
a. homogenous hydrated matrix resists compressive forces, constantly recycled, secrete
smaller molecules with age
b. collagenous fibers (15-20%) network resists tension and maintains shape
c. ex. articular cartilage at joints, costal cart of ribs, trachea and bronchi, nose end
3. Fibrous - very strong and durable, low flexibility
a. dense interwoven bundles of collagenous fibers provide tensile strength (prevent
exploding*) and resist tension
b. ex. intervertebral discs*, pubic symphysis, insertion of tendons or ligaments to bone
Bone Tissue
Bone cells:
1. Osteochondrial progenitor (osteoprogenitor) cells - unspecialized mesenchymal (stem) cells
a. mitotic cells, can produce osteoblasts and chondroblasts
2. Osteoblasts - bone-forming cells located at edges of bones
a. secrete organic matrix including collagenous fibers
b. establish conditions favorable for calcification
c. nonmitotic, convert to osteocytes when surrounded by calcified matrix
d. also strips off organic matrix on outside of bone for osteoclasts to resorb bone tissue
3. Osteocytes - mature bone cells in lacunae surrounded by calcified matrix
a. processes extend through canaliculi to form gap junctions with other processes, allows
movement of nutrients and gases
b. do not form organic matrix but do recycle inorganic matrix
4. Osteoclasts - large motile multinucleated cells at bone edges that break down bone
a. ruffled border secrete acids and enzymes that dissolve inorganic and organic matrix
b. derived from common precursor of monocytes and macrophages
Bone matrix:
1. Organic matrix - strong and tough/flexible
a. collagen fibers in parallel arrays in lamellar bone, random orientation in woven bone
b. amorphous proteoglycan ground substance including chondroitin sulfate
2. Inorganic matrix - hard/stiff and brittle
a. calcium phosphate crystals called hydroxyapatite {Ca10(PO4)6(OH)2}
b. deposited to reflect organization of organic matrix particularly collagen fibers
3. Final properties of bone tissue result from proportions of organic to inorganic matrix
a. ex. nonweight-bearing bones can have more inorganic matrix (genetic)
Bone density:
Differs in amount of matrix and the amount of marrow spaces.
1. Woven bone - collagen fibers are randomly oriented, initially formed in fetus or at fractures,
remodeling converts it into compact or cancellous bone
2. Compact bone - densely packed bony substance arranged in regular lamellae in osteons
o Compact bone is thickest where stresses are most aligned. In the diaphysis both axial
compressive forces and tension (stretch) occur along the longitudinal axis; osteons run
parallel to long axis.
o Osteon or Haversian system (figure in class)
 Central canal - contains longitudinal running vessels & nerves
 Concentric lamellae - circular
 Osteocytes in lacunae
 Canaliculi - thin channels connect lacunae with central canal and each other,
cytoplasmic processes of osteocyte extend through
 Perforating canals (Volkmann's canal) - horizontal canals between adjacent
central canals
 Interstitial lamellae - fill gaps between osteons
 Circumferential lamellae - follow outer contours of bone, added by appositional
growth
3. Cancellous bone or spongy bone - lamellae with osteocytes but no osteons, bone arranged in
plates or struts called trabeculae with many large irregular marrow spaces
o Trabeculae arranged in latticework and oriented along stress lines, cross-bracing
prevents buckling during compression, withstand stresses from many directions
(bending). Trabeculae withstand large loads without excessive amounts of bone tissue,
which reduces weight, spaces contain red marrow
Bones classified by shape:
1. Long bones - longer than wide, shaft with two ends, predominately compact bone
2. Short bones - length equals width, primarily spongy bone, ex. carpals and tarsals
3. Flat bones - thin and flat, layer of spongy bone sandwiched between two thin layers of compact
bone, ex. cranium, sternum, ribs, and scapula
4. Irregular bones - complex shapes, ex. vertebrae & middle ear bones
5. Sutural (Wormian) bones - small variable bones formed along cranial sutures, individual
variability
6. Sesamoid bones - small bones formed in tendons, variable in number, ex. patella
Long bone structure
(figure in class)
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Diaphysis - shaft, mostly compact bone
Epiphysis - ends, mostly cancellous bone, contains red bone marrow
Articular cartilage - hyaline cartilage on joint surfaces to reduce friction
Periosteum - outer dense fibrous c.t. covering bone surface except articular cart, continuous with
tendons via perforating (Sharpey's) fibers (collagen fibers embedded in bone lamellae)
o inner osteogenic layer contains vessels, osteoprogenitor cells, osteoblasts, and
osteoclasts
Medullary cavity - large central cavity containing yellow bone marrow (lipid reserve) in adult
bones, in fetal bones RBC are also produced
Endosteum - connective tissue layer lining medullary cavity, containing osteoprogenitor cells,
osteoblasts and osteoclasts
Nutrient foramen - opening allowing vessels to enter bone
Epiphyseal plate/line - area where diaphysis connects to epiphysis
Metaphysis - columns of spongy bone that unites epiphyseal plate to diaphysis
Bone Formation and Remodeling
Endochondrial ossification
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bones preformed in hyaline cartilage and cartilage is replaced by bone
process occurs while maintaining supportive function of skeleton
occurs in most bones, follows genetic template
Process
1. Mesenchymal cells cluster and differentiate into chondroblasts, which form a cartilaginous matrix.
Cartilage is surrounded by perichondrium with chondroblasts.
2. Cartilage enlarges by interstitial and appositional growth
3. Osteoprogenitor cells in the perichondrium become osteoblasts and deposit a thin collar of
compact bone around diaphysis; the perichondrium is now called periosteum.
4. Chondrocytes beneath the collar and in midshaft hypertrophy and lacunae expand, reducing the
amount of matrix. Chemical changes cause the matrix to calcify, which limits diffusion and
chondrocytes die. Empty lacunae merge to form small cavities within calcified matrix.
5. Vessels and osteoprogenitor cells grow into calcified cartilage of diaphysis forming an osteogenic
bud, which forms osteoblasts that secrete bone matrix over the surfaces of calcified cartilage
matrix producing trabecular bone.
6. In center of diaphysis osteoclasts resorb trabecular bone to form medullary cavity. Called Primary
Ossification Center (POC)
7. Secondary Ossification Centers form in the epiphyses later by same sequence: hypertrophy,
calcification, replacement, but there is no collar and bone remains trabecular. The A band of
articular cartilage and the epiphyseal plate of cartilage remains.
Epiphyseal plate is responsible for growth in diaphyseal length. Cartilage formation occurs at epiphyseal
side and bone formation at diaphyseal side.
Zones:
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Resting cartilage - anchors plate to bone
Proliferating cartilage - mitotic, chondrocytes form stacks of cells
Hypertrophic cartilage - cells and lacunae enlarge, matrix reduced
Calcified cartilage - matrix calcifies and chondrocytes die
Ossification - vessels and osteoprogenitor cells invade, form osteoblasts and deposit bone matrix
on calcified cartilage
When activity of Zone 2 is less than Zone 5 growth stops and plate becomes epiphyseal line
Articular cartilage is responsible for growth of epiphyses. Functions like epiphyseal plates but zones are
not as obvious and articular cartilage never ossifies.
Bone diameter and bony projections are formed by appositional bone growth in periosteum.
Intramembranous ossification
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occurs in collagenous connective tissue membrane, no cartilage involved
forms flat bones of skull, part of mandible, and clavicular diaphysis
Process:
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Area becomes highly vascularized with large number of osteoprogenitor cells
Osteoprogenitor cells cluster and differentiate into osteoblasts
Osteoblasts deposit organic matrix with collagen fibers followed by calcification
Osteoblasts surrounded by calcified matrix become osteocytes in lacunae
Clusters form calcified spicules, which continue to elongate and fuse together to form a trabecular
latticework or are remodeled into compact bone around vessels
6. Periosteum forms on outside and endosteum on inside surfaces, non-ossified membrane
between is called fontanel
7. Growth and remodeling of flat bones are result of bone resorption by osteoclasts and bone
formation by osteoblasts in coordinated fashion.
a. ex. deposition on outer surface and edges with resorption on inner surfaces of a bone
Bone Remodeling and Repair
Remodeling is a combination of osteoblasts building bone and osteoclasts breaking down bone. Normal
bone maintenance requires balanced activity of both cell types. Increasing or decreasing the activity of
one cell type will increase or decrease the amount of bone present.
1. Functional adaptation - bone tissue will remodel to resist mechanical stresses applied to the
bone, ex. exercise increases osteoblast activity producing thicker bones and larger sites for
muscle attachment
2. After a long bone fracture, an internal callus and an external callus largely of cartilage form,
endochondrial ossification occurs and remodeling reforms the bone shape
Divisions of the skeletal system
1. Axial skeleton - skull and hyoid, vertebral column, ribs, sternum
2. Appendicular skeleton - scapula and clavicle, arms, pelvis, legs
Tooth Formation
Figure in class
Enamel
large dense hydroxyapatite crystals embedded in insoluble protein fiber network
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Very hard and resistant
Small amount of mineral exchange with saliva
Fluoride produces enamel 3X more resistant to caries in children
Formed by special epithelial cells prior to tooth eruption
Dentin
hydroxyapatite crystals embedded in strong meshwork of collagen fibers
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Similar to bone but without cell, vessels and nerves
Mineral deposition and resorption are about 1/3X of bone
Deposited, nourished and maintained by odontoblasts lining pulp cavity wall
Cementum
almost identical to bone including cells
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Mineral exchange same as bone
Collagen fibers extend from cementum into jaw bone to hold tooth in place
Formed by cells of periodontal ligaments lining tooth socket
Pulp - connective tissue with nerve, vessels, lymphatics
20 deciduous teeth (erupt 6 mon-2 yrs), 28-32 permanent teeth
Fetal tooth formation process:
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Epidermis of oral cavity grows into jaw mesenchyme and forms tooth bud (figure in class)
Outer layer of bud forms enamel
Inner layer of bud forms dentin
Crown is produced first, root next and cementum laid down
As teeth develop and jaw bone ossifies, teeth become surrounded by bony socket
As root elongates and bone ossifies, crown is pushed through the gum
Permanent teeth formed in same manner, stalk forms lateral bud that lies lingual to deciduous
teeth
As permanent teeth grow, deciduous roots are reabsorbed and only crown with upper root are
shed
All molars are permanent teeth (1-3)
Rate of development and eruption increased by thyroid and growth hormones
Early salt deposition affected by availability of Ca and PO4 and vitamin D, and rate of parathyroid
secretion
Calcium Metabolism
Calcium - necessary for blood clotting, normal cardiac and skeletal muscle contraction, nerve function,
and enzyme cofactor
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30% increase in free Ca, nerves and muscles become unresponsive
35% decrease, nerves over-excitable and convulsions occur; 50% fatal
Sources
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bones and teeth provide huge reservoir of Ca
98-99% Ca filtered from blood in kidneys is reabsorbed
10-20% Ca consumed as food is absorbed by brush border of intestinal cells
Distribution in the body:
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99% deposited in bones and teeth
0.5% bound to plasma proteins in blood
0.5% free ionized calcium in extracellular fluid
Endocrine regulation of calcium:
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Parathyroids are small glands on posterior surface of thyroids, stimulated by low free Ca levels,
secrete parathyroid hormone (PTH)
Thyroid glands wrap around anterior trachea below the larynx, stimulated by high free Ca levels,
secrete calcitonin (CT)
Process of calcium regulation:
(figure in lecture)
1. Slight decrease in free ionized Ca level stimulates receptor cells in parathyroid, turns on gene to
produce PTH and release it
a. PTH increases number and activity of osteoclasts, which increases bone resorption
(cAMP mechanism)
b. PTH increases Ca reabsorption by kidneys and HPO3-2 excretion in urine (cAMP
mechanism)
c. PTH facilitates formation of calcitriol (hormone) from Vitamin D by kidneys and liver
i.
calcitriol increases Ca absorption in intestines
ii.
calcitriol increases Ca reabsorption by kidneys
iii.
calcitriol increases number of osteoclasts
d. Result of above activities is an increase in free ionized Ca level
e. Regulation by negative feedback on free Ca levels, half-life of PTH = 20 min
2. Slight increase in free ionized Ca level stimulates parafollicular cells of thyroid glands to release
calcitonin
a. CT decreases bone resorption by inhibiting osteoclast activity
b. CT increases kidney excretion of Ca
c. Result is a decrease in free ionized Ca levels
d. Regulation by negative feedback on free Ca+2 levels, half-life of CT = 10 min
e. Less active in adults, may limit bone loss in pregnant women
3. Other hormones e.g., Growth h, Thyroid h, Estrogens and Testosterone have some effects on Ca
metabolism
Articulations and Movement
Articulation
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site of union or junction between two or more bones, point of contact
compromise between strength & mobility
Functional classification of joints by mobility:
1. Synarthroses - immovable, result of two separate ossification centers
a. direct union of opposing surfaces or continuous fibrous c.t. connection
b. no joint cavity
c. ex. Sutures - irregular interlocking margins of skull bones
 Gomphosis - tooth in socket
 Synchondrosis - rigid cartilage bridge between two bones; epiphyseal plate,
sternal ribs
2. Amphiarthroses - partial movement
a. union by ligaments and possibly interposed fibrous cartilage pad
b. partial joint cavity in cartilage pad
c. hyaline cartilage covering articular surfaces
d. ex.
 Syndesmosis - ligament at distal ends of tibia and fibula
 Symphysis - intervertebral disc, pubic symphysis
3. Diarthroses - free movement
a. complex joint with joint capsule, ligaments and pads (cartilage or fat)
b. joint cavity lined with synovial membrane and filled with synovial fluid
c. ligaments form walls of cavity, hyaline cartilage covers articular surfaces
d. ex. Majority of joints - ankle, knee, hip, shoulder, elbow, wrist, head
Figures in class
The greater the freedom of movement, the greater the chance of dislocation.
Range of movement at a joint is determined by:
1. extensibility of muscles - typical muscle is attached to two bones (origin and insertion) across
movable joint
2. extensibility of ligaments - strong, collagen fibers, stabilize joint and limit excessive movement
3. architecture of joint surfaces - “fit”
4. elasticity of articular capsules and fluidity of pads
5. resistance of surrounding tissues
Muscular System
The following topics will be covered in this category.
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Muscle Types
Whole Muscle Mechanics
Skeletal Muscle Microscopic Anatomy
Muscle Contraction
Muscle Types
Major functions
1. Movement - all 3 types of muscle
2. Maintain posture - skeletal muscle
3. Heat production - skeletal muscle
Characteristics of muscle tissue
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Excitability - ability to respond to stimuli
Contractility - ability to shorten forcefully
Extensibility - ability to stretch
Elasticity - ability to return to original shape and length
In the following lectures, identify the structures that contribute to these four characteristics of
muscle tissue.
Muscle tissue composes 40-50% of total body weight. There are three types of muscle: smooth muscle
found in the walls of the viscera, cardiac muscle found only in the heart, and skeletal muscle associated
with bones. We will compare the three types of muscle according to the following categories:
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2.
3.
4.
Gross muscle arrangement - indicates how contractile force is applied
Connective tissue framework and vascular supply - indicates activity level
Innervation - affects type and speed of contraction
Fiber structure and cell shape - determines physiology
Smooth Muscle
1. Occurs in small groups (ex. arrector pili) or sheets of overlapping cells tightly bound together (ex.
digestive tube, uterus, bladder, respiratory tract, vessels), can regenerate.
2. Sparse reticular and collagenous c.t. network, no tendons, sparse capillary network
3. Two types of innervation:
a. Multiunit innervation - motor units with each muscle cell innervated by one or more motor
neurons, produces rapid coordinated contraction. ex. ductus deferens, ciliary body and
iris, arrector pili, large arteries
b. Visceral innervation - one motor neuron innervates several cells, muscle cells connected
by gap junctions, produces a wave of contraction (peristalsis). Contraction can also be
caused by hormones, stretching, and some chemicals. In absence of stimulation smooth
muscle shows rhythmic cycles of contraction.
4. Spindle-shaped cells with one central nucleus; unstriated, no myofibrils, scattered myosin
filaments, actin filaments attached to dense bodies in network of intermediate fibers (desmin),
adjacent cells connected by dense bodies. Contraction produces a cellular twisting motion.
Action is slower but longer lasting, aerobic, resist fatigue.
Cardiac Muscle
1. Branching network of cells forming layers that wind in overlapping spirals to form heart. Cells
connected by intercalated discs containing desmosomes and gap junctions.
2. Loose c.t. with extensive capillary beds. A c.t. layer separates atria from ventricles.
3. Inherent rhythmic contraction, pacemaker cells, gap junction connections form functional
synsytium of the two atria and of the two ventricles, heart rate moderated by ANS.
4. Branching cells with one or more central nuclei, striated, actin and myosin in myofibrils, aerobic
metabolism of lipids and carbohydrates, resist fatigue.
Skeletal Muscle
1. Bundles of cylindrical fibers (cells) run in parallel (fascicle); in various arrangements such as
spindles, bands, or sheets; typically between two bones and across a joint
2. Connective tissue subdivided into three parts which together form part of the deep fascia, also
merge to form tendons and aponeurosis. Very vascular.
a. Endomysium - thin c.t. layer with capillaries surrounding fiber, includes satellite cells
(stem cells) involved in muscle repair
b. Perimysium - c.t. layer of collagenous and reticular fibers with vessels surrounding
fascicle
c. Epimysium - dense c.t. layer surrounding groups of fascicles and entire muscle
3. Motor unit - functional unit of muscle, consists of a motor neuron and all muscle fibers it
innervates. Degree of muscle contraction depends on number of active motor units or
recruitment
4. Long multinucleate cylinders with peripheral nuclei; striated, actin and myosin arranged in
myofibrils.
Whole Muscle Mechanics
Muscle twitch
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Contraction of one muscle fiber in response to a single stimulus
Twitches in different muscles can vary in duration<
Myogram - record of muscle fiber contraction
o Latent period - time between stimulus and when contraction begins, Ca+2 release (2
msec)
o Contraction period - shortening, produces maximum tension (10-100 msec)
o Relaxation period - lengthening, active transport of Ca+2 (10-100 msec)
Figure in class
All or None Principle
A muscle fiber at a given resting length, when stimulated to contract, always produces the same amount
of tension.
Variation in the amount of tension produced in a whole muscle is determined by:
1. Frequency of stimulation - internal and external tension
2. Number of muscle fibers stimulated or recruitment
Stimulation Frequency (figures in lecture)
Normal activities require more tension than is produced by single fiber twitch, in fact they involve
sustained muscle contractions within the whole muscle
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Wave summation - if 2nd stimulus is applied before relaxation is complete, the second contraction
is greater
Tetanus - at higher frequency of stimulation muscle relaxation between contractions is reduced
 Incomplete tetanus - producing peak tension during rapidly alternating cycles of
contraction and partial relaxation
 Complete tetanus - sustained maximal contraction at peak tension, typical of normal
muscle contraction
Treppe - relaxation is complete before next stimulus occurs, each contraction is a little stronger
than previous. Physiological efficiency improves because of temperature rise and gradual
increase in Ca+2 in sarcoplasm. Basis for warm-up.
Effects of internal tension and external tension during muscle contraction
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Internal (active) tension - force generated in individual muscle fibers by myofibrils
External (passive) tension - force generated in the connective tissue and tendons of the whole
muscle
o Muscle fibers are surrounded by connective tissue layers which are continuous with the
tendons that attach to bones. Connective tissues are flexible and elastic, called series
elastic elements
Process: Internal tension is applied to the series elastic elements, which stretch, stiffen and then
transfer tension to the resistance. During summation external tension gradually climbs to level of
internal tension. (Demonstration in class)
Muscle fiber recruitment
The amount of tension produced in a whole muscle is also determined by the number of muscle fibers
stimulated, called recruitment. Muscle is composed of many muscle fibers each belonging to a motor
unit.
a. Motor unit - all muscle fibers that are innervated by a single motor neuron
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When stimulated muscle fibers contract maximally for conditions (All or None Principle)
Amount of whole muscle tension is determined by number of muscle fibers contracting, this is
controlled by number and size of motor units functioning at one time
Small fast-reacting fine-control muscles have few muscle fibers per motor unit, large slower
muscles have many fibers per motor unit
Gradation of muscle contraction is achieved by multiple motor unit summation, begins with small
motor units and then adds larger motor units
Muscle fibers of a motor unit are typically distributed throughout the fascicles of a muscle
producing uniform contraction whether weak or strong
Smoothness of contraction is a function of motor units in the muscle firing asynchronously to
prevent fatigue of fibers or jerky action
Tone is the involuntary activation of a small number of motor units that give firmness to relaxed
muscle
Characteristics of contraction
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Isotonic contraction - when a muscle contracts the external tension gradually increases to peak
level, slightly exceeding the resistance and causing a change in muscle length. Causes changes
in shape of muscle
o Concentric contraction - tension increases as muscle shortens
o Eccentric contraction - tension is maintained as muscle lengthens
Isometric contraction - when a muscle contracts the peak tension produced is less than
resistance and no significant muscle shortening occurs. Contraction and stretching (gravity) are
equal and opposing forces that create tension but no muscle shortening. Produces no movement
but stabilizes joints and maintains posture, uses energy. ex. holding book
Speed of muscle contraction - the heavier the resistance, the longer the muscle takes to reach
peak tension and start to shorten, and the less the muscle will shorten. For any given resistance
there is an optimal combination of tension and speed for each muscle.
Fatigue - nerve impulses arrive but muscle contractions become weaker because of ACh
depletion or buildup of metabolic wastes and depletion of ATP
Muscle Energetics
1. Resting muscle
a. ATP is produced by aerobic metabolism of fatty acids faster than needed
b. Excess is used to produce creatine phosphate
2. Contracting muscle
a. Normal stores of ATP last a few seconds (each thick filament uses about 2500 ATP
molecules/sec)
b. Then muscle switches to aerobic metabolism of pyruvic acid from glucose, stored
glycogen, and fatty acids
3. Peak muscle activity
a. There is insufficient O2 available and muscle switches to anaerobic metabolism of pyruvic
acid from glucose and stored creatine phosphate
b. Creatine phosphate can transfer a high energy P to ADP to form ATP, extending activity
for 15 sec
Types of Cellular Respiration:
1. Aerobic respiration
a. For moderate activity longer than 30 sec (marathon is 100% aerobic)
b. Fatty acids, glucose or glycogen is broken down into pyruvic acid that is used by
mitochondria to form ATPs
c. Slower than glycolysis but yields more ATP (36 net/glucose molecule)
d. Monosaccharides preferred but can also break down fatty acids and amino acids
e. Aerobic requires oxygen and is limited by oxygen availability, oxygen in blood is bound to
Hb and in muscle is bound to muscle myoglobin
2. Anaerobic respiration
a. Up to 3 min supply at maximal muscle activity (aerobic respiration continues to produce
about 30% of ATP consumed)
b. Glucose or glycogen is broken down into pyruvic acid in a series of reactions called
glycolysis in the muscle cytoplasm (2 ATP net/glucose molecule). Pyruvic acid is formed
too rapidly for mitochondria to use and is converted into lactic acid which diffuses out of
the muscle
c. Anaerobic requires no oxygen
d. Cori cycle
a. During maximal activity lactic acid accumulates in blood and muscle (oxygen
debt)
b. When oxygen is available lactic acid is converted back into pyruvic acid in the
liver and then into glucose and is returned to skeletal muscle to be stored as
glycogen
In skeletal muscle there is different muscle fiber types specialized for different forms of respiration.
Skeletal muscle fiber types:
Type I, Red slow-twitch fibers - contract slowly and fatigue slowly
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small diameter cells
aerobic with many mitochondria, low glycolytic enzymes
very vascular (O2), high myoglobin levels (binds O2)
metabolism of lipids and carbohydrates, some amino acids
Endurance activities, marathon, swimming, jogging
Type IIx, White fast-twitch - contract fast and fatigue quickly
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large diameter cells, most common
anaerobic with few mitochondria, high glycolytic enzymes
less vascularized, low myoglobin levels
store glycogen, metabolism of carbohydrates
Dashes and sprints, weight lifting, throwing ball
Type IIa, Intermediate fibers - contract fast and fatigue relatively slowly
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intermediate diameter cells
anaerobic with intermediate number of mitochondria, high glycolytic enzymes
intermediate vascularization, low myoglobin
store glycogen, metabolism mainly carbohydrates
Increase favors endurance activities
Percentage of red and white fibers in a muscle is genetically determined, training can convert white fasttwitch (IIx) into intermediate fibers (IIa) and cause muscle hypertrophy (fiber enlargement, but not
increase in fiber number).
Smooth Muscle Contraction
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No T-tubules, gap junctions are present
Sarcoplasmic retiiculum is a loose network. Calcium enters sarcoplasm from SR and ECF and
binds with calmodulin protein, no troponin.
Actin and myosin myofilaments overlap forming scattered bundles. Calmodulin-Ca activates
myosin kinase, which transfers a phosphate from ATP to myosin and crossbridges form.
Contraction produces a cellular twisting motion.
Relaxation: myosin phosphatase removes phophate from myosin
Skeletal Muscle Histology
Muscle fiber structure
Long, cylindrical, multinucleated cell containing usual intracellular organelles but in a unique arrangement
1. Sarcolemma - plasma membrane of muscle cell
a. Attached to collagen fibers of tendons
2. Sarcoplasm - cytoplasm of muscle cell including mitochondria and glycogen granules
3. Sarcoplasmic reticulum - modified ER of muscle cell
a. Longitudinal system of membranous tubules and cisternae surrounding myofibrils
b. Functions in calcium storage (Ca+2 release channels) and muscle metabolism
4. T-tubule system - infoldings of sarcolemma at A-I junction
a. Produces extension of extracellular space into fiber, encircle myofibrils and filled with
ECF
b. Provides for rapid conduction of nerve impulses into and throughout the fiber
5. Myofibrils - long, cylindrical contractile fibril composed of filaments (striations)
a. Attached at ends of sarcolemma and runs the length of the cell
b. Sarcomere - repeating functional unit of myofibril, 10,000 sarcomeres/myofibril
Myofilament structure
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Myosin - contractile muscle protein
o Helical rod (light meromyosin), points toward M-line
o
o
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Hinge capable of swiveling
Globular head (heavy meromyosin) can form crossbridges with actin filaments, projects
outward
Actin - contractile muscle protein
o F-Actin in the form of two twisted strands
 Composed of G-actin monomers
 Each monomer has a myosin binding site
 Central strand of nebulin holds monomers in place
o Tropomyosin strands encircle the F-actin strands covering myosin binding sites
o Troponin molecules are scattered at regular intervals along the tropomyosin
 Contains three subunits, binding to tropomyosin, G-actin, and calcium
Myofibril structure
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Z-line - forms boundaries of sarcomere
o Perforated disc holds thin filaments in place
o Desmin intermediate filaments connect adjacent myofibrils
I-band - composed of thin actin filaments only
A-band - composed of thick myosin filaments including overlapping actin
o Elastic filament - composed of titin, anchors thick filaments to Z-lines, acts like spring
and is responsible for extensibility and elasticity
H-zone - in center of A-band, contains only thick filaments
M-line - in center of H-zone, cross-connections between adjacent thick filaments
Relaxed condition: (figure in class)
Contracted condition: A-band remains constant length, I-band shortens. What happened?
Muscle Contraction
Excitation-Contraction Coupling Mechanism
Nerve impulse at neuromuscular junction induces muscle contraction.
Process:
1. Nerve impulse reaches the synaptic terminal causing the nerve's synaptic knobs to release
acetylcholine, ACh crosses the synaptic cleft and binds to the motor endplate receptors causing a
depolarization that travels over the sarcolemma and down into the T-tubule system
2. Impulse travels to SR cisternae and causes Ca+2 release channels to open briefly, Ca+2 flows out
into sarcoplasm
3. Increase of Ca+2 above 10-6M exposes binding sites on actin filaments (1 msec)
4. Sliding filament mechanism
5. Impulse ends and Ca+2 release channels close
6. Ca+2 active transport pumps return Ca+2 to SR or into ECF. Requires ATP expenditure
7. When Ca+2 level falls below 10-6M, myosin binding sites on G-actin are covered and crossbridges
cannot form
Sliding Filament Mechanism
Sliding is produced by making and breaking crossbridges between actin and myosin. Myosin heads link to
actin, swivel pulling actin filaments toward H-zone, disconnect and reconnect. Each cycle shortens
muscle length.
Process:
1. Relaxed muscle: ATP attaches to myosin heads, which act as ATPase splitting ATP into ADP +
P . Myosin heads are activated or cocked
2. When SR releases Ca+2 , it combines with a troponin subunit and weakens the troponin-actin
bond, troponin moves pulling tropomyosin away and exposes myosin binding site on G-actin
monomers
3. Activated (cocked) myosin heads spontaneously bind to exposed myosin binding site on G-actin
forming crossbridges
4. Power stroke: Myosin heads swivel (conformational change), which pulls actin filaments toward
H-zone, then myosin releases the ADP + P
5. New ATP binds to myosin heads causing heads to detach from actin filaments and heads swivel
back to their original position (conformation change) as ATPase splits ATP
Length-Tension Relationships
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Amount of tension generated during contraction depends on the number of crossbridges (on all
sarcomeres of myofibril) that can form and is based on the degree of overlap of actin and myosin
in resting muscle
Resting muscle length (see figure in text)
 At short sarcomere lengths there is too much overlap, actins collide and interfere with
each other, myosin hits Z-line
 At long sarcomere lengths too little overlap reduces number of potential crossbridges
 At about normal resting length the maximal number of crossbridges form producing
highest tension
Muscle Relaxation
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Result of active transport of calcium back into the SR (Steps 6 and 7 above), requires ATP
Muscle Lengthening
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Passive process, no active mechanism for returning muscle fibers to normal resting length
Depends upon:
1. Elastic forces of extracellular fibers in tendons and connective tissues called series
elastic elements
2. Antagonistic muscle contraction
3. Gravity
Nervous System
The following topics will be covered in this category.
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Neurons
Neuron Resting Potential
Neuron Action Potential
Synaptic Transmission
Sensory Receptor Function
Vision
Hearing, Taste, & Smell
Hindbrain
Midbrain
Forebrain
Spinal Cord Structure
Spinal Reflexes
Autonomic Nervous System
Neurons
Nervous System
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CNS contains brain and spinal cord
PNS contains cranial and spinal nerves
Neuroglial cells - do not generate or conduct impulses; support, nurture and protect neurons, smaller,
more numerous, mitotic
Types:
1. Astrocytes - star shaped, in CNS, maintain K+ balance, link neurons and vessels forming bloodbrain barrier that regulated passage into brain
2. Oligodendrocytes - most common, produce myelin sheath around axons in CNS
3. Microglia - form from monocytes, phagocytic cells (microbes and debris) in CNS
4. Ependyma - line CSF-filled cavities of CNS and filter CSF
5. Satellite cells - surround and support ganglionic cells in PNS
6. Schwann cells - produce myelin sheath around axons of PNS neurons
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Unmyelinated axons - covered by a thin layer of glial plasma membrane
Myelinated axons - have a thick myelin sheath composed of lipid and protein (myelin), acts as
insulating layer
 Schwann cell membrane wraps around the axon many times; nucleus and cytoplasm
form outermost layer or neurolemma which provides regeneration tube
 Nodes are uncovered areas between Schwann cells
Neurons - convert stimuli into nerve impulses (excitability)
1. Soma - cell body with typical plasma membrane and cell organelles
2. Dendrites - highly branched generally short cytoplasmic processes, receive input
3. Axons - long thin process, send impulse
a. Originates on axon hillock of soma, initial segment contains trigger zone, with
neurofilaments for transport
b. Axon collaterals - side branches
c.
Terminates in many fine filaments or axon terminals with synaptic knobs containing
synaptic vesicles
d. Limited mitosis, new cells form in hippocampus of humans
Neurons classified by number of processes:
1. Unipolar - one bifurcated process, dendrites and axon are continuous, sensory neurons
2. Bipolar - two processes, one dendritic and one axonic, special senses neurons
3. Multipolar - more than two processes, one axon and several dendrites, motor neurons
Neuron Resting Potential
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There is a potential difference across the membranes of most cells, with the inside of the cell
negative relative to the outside of the cell. Called resting membrane potential. Ranges from -9 to
-100mV.
Distribution of ions across the membrane and membrane permeability are responsible for the
potential difference across the membrane. This charge difference is only in the fluid close to the
membrane.
Distribution of some ions in ICF and ECF
Ions
ICF
ECF
K+
400
10
Na+
50
460
Cl-
40-100
540
Polyanions-
345
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Ionic conc. in squid axon and ECF, (Lowey and Siekevitz)
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Distribution is the result of a diffusion gradient and an electrical gradient for each ion.
1. Following its concentration gradient, K+ will diffuse out through leakage channels. But the
electrical gradient runs in the opposite direction causing K+ to move in. The two forces
reach an equilibrium with slightly more negative charges inside than outside.
2. Following its concentration gradient, Na+ will diffuse in through leakage channels. The
electrical gradient runs in the same direction also causing Na+ to move in. There is no
gradient to force Na+ out. Cl- follows Na+ but is repelled by the cell's negative charge.
3. Membrane permeability for K+ is greater than for Na+, therefore K+ diffuses out faster than
Na+ diffuses in.
4. Polyanions are too large to leave the neuron in any quantity.
5. Na+-K+ pumps maintain the concentration gradients. Active transport process pumps
3Na out for every 2K transported in.
Figure in class:
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Resting membrane potential - a polarization or electrical difference between the inside and
outside of inactive cells caused by concentration differences of certain ions and selective
membrane permeability.
Graded potential - small deviation from the resting membrane potential caused by a stimulus.
1. Localized, no refractory periods
2. Varies in amplitude and is directly related to the number of voltage-gated Na channels
open
3. Hyperpolarization - more negative than resting potential
4. Depolarization - less negative than resting potential
Neuron Action Potential
All or None Principle - if the graded potential causes a threshold level depolarization, action potentials will
be generated in the neuron.
Action potential
1. Rapid depolarization
a. Graded potential that reaches threshold causes many voltage-gated Na+ channels to
open (in addition to Na+ leakage channels) and voltage-gated K+ channels to begin to
open
b. Membrane becomes more permeable to Na+, which rapidly diffuses into the axon
c. Na+ influx carries positive charges into the axon and decreases potential difference until
polarity is reversed.
2. Repolarization
a. Membrane returns to normal Na+ permeability as voltage-gated Na+ channels close
(+30mV) and are inactivated (cannot reopen)
b. Voltage-gated K+ channels open more slowly and now allow K+ to diffuse out of the cell
along its electrochemical gradient
c. K+ efflux carries positive charges out of the axon and increases the potential difference
d. During repolarization, voltage-gated Na+ channels are closed but no longer inactivated
e. Voltage-gated K+ channels begin to close at resting membrane level resulting in slight
hyperpolarization or afterpotential
3. Na-K exchange pump returns concentrations of Na+ and K+ to resting state levels
4. Absolute refractory period
a. Time during which a second stimulus cannot produce an action potential
b. Voltage-gated Na+ channels already open or are inactivated
5. Relative refractory period
a. Time during which only a second very strong stimulus produces an action potential
b. Voltage-gated Na+ channels are closed but no longer inactivated
6. Figure in class (see Figure in text)
T0 = resting membrane pot
T1 = depolarized
T2 = reverse polarity
T3 = repolarized
T4 = hyperpolarized
Absolute refractory period
Relative refractory period
Propagation of action potential - self-propagating change in polarity along an axon
1. Na+ flows into the axon and depolarization begins at the axon hillock
2. Na+ flows into adjacent areas causing a graded depolarization or local current
3. In adjacent axon area the graded depolarization causes voltage-gated Na+ channels to open and
Na+ diffuses in. (Axon hillock does not respond to a local current.)
4. Process continues as a chain reaction or wave of depolarization along the axon
5. Depolarization wave is followed by a wave of repolarization and then a wave of refraction, thus
the action potential only travels in one direction
Continuous propagation - action potential moves in series of small steps along the unmyelinated axon
Saltatory propagation - action potential jumps from node to node along the myelinated axon, 5-7X faster,
uses less ATP energy
Propagation speed:
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Myelination - myelinated axons conduct faster than unmyelinated axons
Axon diameter - larger diameter axons conduct faster than smaller diameter axons
 Type A fibers: 4-20 µm axon diameter, myelinated, 15-120 m/sec
 Type B fibers: 2-4 µm axon diameter, myelinated, 3-15 m/sec
 Type C fibers: less than 2 µm axon diameter, unmyelinated, 0.5-2 m/sec
Synaptic and Junctional Transmission
Transmission of impulses between nerves or nerves and muscle or gland
Types of transmission:
1. Electrical synapse or Gap junction - action potential passes directly from cell to cell, connexon
proteins form tunnel that connects cells' cytoplasm, 2-way transmission, allows for
synchronization of activity, faster than chemical, occurs in smooth and cardiac muscle
2. Chemical synapse - action potential produces a chemical signal that crosses the space and
produces a new action potential, 1-way, allows for modification
Chemical Synapse
Transmission is not jumping of action potential but a complex chemical process permitting grading and
modulation (frequency change) of neural activity
Components of chemical synapse:
1. Presynaptic neuron - neuron sending the impulse
a. Axon of presynaptic neuron terminates on the soma or dendritic region of the
postsynaptic neuron
b. Axon ends in terminal branches with synaptic knobs that contain many mitochondria and
vesicles of a chemical neurotransmitter
c. Number of knobs per cell varies, (1-40,000)
2. Synaptic cleft - space between cells across which an impulse must be transmitted
a. No direct connection, about 20-50 nm space between presynaptic and postsynaptic
3. Postsynaptic neuron - neuron receiving impulse
a. Neurotransmitter produces the action potential
b. Divergence - axon divides into many terminal branches and projects to many
postsynaptic neurons
c. Convergence - neuron may receive input from thousands of other neurons
i.
Oscillating circuit - neuron provides positive feedback to presynaptic neurons,
prolongs response to stimulus
Transmission process
1. Presynaptic action potential causes voltage-gated Ca+2 channels to open in synaptic knobs
a. Ca+2 diffuses in along its concentration gradient
b. Ca+2 stimulates exocytosis of vesicles and releases neurotransmitter into the cleft
2. Transmitter diffuses across cleft
a. Synaptic delay (0.2-0.5 msec) - time between presynaptic action potential and PSP
b. Fewer synapses produce shorter delay
3. Transmitter binds to receptor sites on postsynaptic and causes Na + channels to open
a. Ligand-activated receptors specific for neurotransmitter
b. Influx of Na+ produces a graded postsynaptic potential (PSP)
c. PSP can be depolarizing (excitatory) or hyperpolarizing (inhibitory)
4. Transmitter removed from cleft
a. By diffusion, enzymatic degradation (e.g. cholinesterase) or cellular uptake (monoamines
by synaptic knobs)
b. Na+ channels close
5. Synaptic fatigue - no neurotransmitter remaining in presynaptic knobs
Integration and modulation at synapse
1. Presynaptic output - by modifying the quantity of neurotransmitter released
a. Facilitation - axon of a 2nd neuron synapses with the presynaptic axon
i.
2nd neuron releases excitatory neurotransmitter that increases number of
presynaptic vesicles of 1st neuron to exocytose
ii.
enhances and prolongs effects on postsynaptic neuron, ex. Serotonin
b. Inhibition - axon of a 2nd neuron synapses with the presynaptic axon
i.
2nd neuron releases inhibitory neurotransmitter that decreases transmitter
released by 1st neuron
2. Postsynaptic input: by summation of PSPs, additive effect
a. Neurotransmitter released from 1 synaptic knob produces a small PSP at one location,
insufficient to produce action potential and gradually decays
i.
Depolarizing PSP is called an Excitatory Postsynaptic Potential or EPSP,
result of chemical-gated Na+ channels opening, lasts about 20 msec
ii.
Hyperpolarizing PSP is called an Inhibitory Postsynaptic Potential or IPSP,
result of chemical-gated K+ or Cl -channels
b. Summation effects
i.
If the sum of EPSPs minus the sum of IPSPs exceeds stimulus threshold then
action potentials will be generated at the initial segment of the axon as long as
the sum is above threshold
ii.
Subthreshold EPSPs and IPSPs decay
iii.
If IPSPs are greater, neuron is unable to generate any action potentials
c. Types of summation
i.
Spatial - large number presynaptic terminals fire at same time
ii.
Temporal - same presynaptic terminals fire in rapid succession
3. Types of neurotransmitters
a. Acetylcholine - ACh, is excitatory at skeletal neuromuscular junction, is inhibitory in vagus
nerve to the cardiac muscle
b. Catecholamines\monoamines - epinephrine, norepinephrine and dopamine can be
excitatory or inhibitory depending on the receptors
c. Amino acids - GABA and glycine are inhibitory in the brain. Glutamate and aspartate are
excitatory
Brain Terminology
Central Nervous System
comprises the brain & spinal cord
Peripheral Nervous System
comprises cranial nerves, spinal nerves, autonomic nervous system
Gray matter
nerve cell bodies mainly in the brain cortex or central spinal cord
White matter
myelinated axons in the brain medulla or outer spinal cord
Terms:
Nucleus
collection of nerve cell bodies inside the CNS but not in the cortex, functional group
Ganglion
collection of nerve cell bodies outside of the CNS
Nerve
bundle of afferent & efferent nerve fibers outside of the CNS
Plexus
network of nerve fibers
Tract
bundle of fibers serving a similar function
Projection area
specialized area of the brain for receiving sensory information from specific body regions &
transmitting motor impulses to specific body regions
Functional classification of neurons:
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Sensory or afferent neurons - carry impulses from receptors to the CNS
o 1st order - from receptor to spinal cord or brainstem
o 2nd order - from spinal cord or brainstem to thalamus, cross-over occurs
o 3rd order - from thalamus to cerebral cortex
Motor or efferent neurons - carry impulses from the CNS to effectors (muscles or glands), always
excitatory in skeletal muscle
Interneuron or association neuron - connects afferent to efferent, excitatory or inhibitory
Somatic
involves skin, skeletal muscle, joints
Visceral
involves internal organs, blood vessels, glands, smooth & cardiac muscle
Divisions of brain:
Forebrain or prosencephalon
cerebrum, thalamus, hypothalamus, pineal body
Midbrain or mesencephalon
small area, only connection between fore & hindbrains
Hindbrain or rhombencephalon
cerebellum, pons, medulla oblongata
Brainstem = mesencephalon + pons + medulla oblongata
Cerebrum - largest region
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Divided into two hemispheres which are subdivided into lobes
o Each hemisphere controls motor functions of opposite side of body
o Hemispheres anatomically similar but functionally different
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Outer cortex of gray matter folded into gyri with deep fissures and shallow grooves (sulci),
increases surface area in a species-specific pattern
Inner medulla composed of white matter, tracts
o Association fibers - connects portions of same hemisphere
o Commissural fibers - interconnect two hemispheres; ex. corpus callosum
o Projection fibers - project into or out of the cortex, forms internal capsule
1. Basal nuclei - masses of gray matter embedded in medulla, areas of synapse
a. Caudate nucleus, lentiform nucleus, globus pallidus, putamen, striatum
b. Input and output between nuclei and the thalamus and then to cerebral cortex
c. Subconscious control of muscle tone, does not initiate movements but coordinates
learned muscle patterns and rhythms
d. Interval timer: Spiny striatal cells receive input from thousands of cortical oscillator cells
with different firing frequencies. Stimulus event causes all oscillator cells to start firing at
same time. Striatal cells record the unique pattern of firing at end of event. When stimulus
happens again, it initiates striatal cell monitoring and dopamine release to start interval
timer
2. Major sensory and motor areas of cortex - central sulcus separates sensory and motor areas
a. Primary motor cortex - surface of precentral gyrus, voluntary motor control, fine
movements of specific muscle groups
b. Premotor cortex - association area, patterns of learned motor responses of sequential
nature
c. Prefrontal area - many associations with other cortical areas, interprets and predicts,
long-term planning and concentration; tension, anxiety and frustration arise here
d. Motor speech center (Broca’s) - coordinates larynx and mouth for speech, develops in 1
hemisphere
e. General interpretive area (Wernicke’s) - integrates sensory information with visual and
auditory memories, only develops in one hemisphere
f. Primary sensory cortex - postcentral gyrus, input from somatic sensory receptors,
localizes origin of sensation on body
g. Primary visual cortex - visual information concerning shape, color and movement
h. Primary auditory cortex - basic characteristics of sound, e.g. pitch and rhythm
3. Hemispheric lateralization - functional differences in two hemispheres
a. Left - language, speech, writing, mathematics, interpretation, reasoning
b. Right - music, artistic skills, spatial skills, imagination and insight, emotional context