Muscle, Bone and Skin

There are three (3) types of muscle tissue:

1) skeletal muscle
2) cardiac muscle
3) smooth muscle

Any muscle generates a force only by contracting its cells. Each muscle tissue, above,
uses a different mechanism to contract.

Muscle contractions have four (4) possible functions:

1) body movement
2) stabilizing body position
3) movement of substance through the body
4) generating heat to maintain temperature (shivering – hypothalamus
controlled)

Recall: Hypothalamus – Regulates body temp and circadian rythmns.

Controls the ANS

Skeletal Muscle
Recall: Epinephrine, which is used by the sympathetic system (“fight or
flight”), dilates this

Skeletal muscle is voluntary muscle tissue that can be consciously controlled, by the
Somatic Nervous system so it uses acetylcholine.

Recall: Somatic Nervous System (SNS).

- The SNS performs all our interactions with the physical world, it is
designed primarily to respond to the external enviromment, such as
control of our limbs and receiving of conscious information
from our senses.

- It contains sensory and motor functions. Its motor neurons

supply nerves ONLY to skeletal muscle.
Ex. shivering

- The cell bodies of somatic motor neurons are located in the

ventral horns of the spinal cord.
a) These neurons synapse directly on
their effectors and use acetylcholine for their
neurotransmitter.
 - The sensory neuron cell bodies are located in the dorsal root
ganglion

- One neuron connects CNS to organ

Skeletal muscle connects one bone to another but the muscle DOESNT directly attach
to the bone. Instead, it is attached to a tendon (tendon connects muscle to bone;
ligament connects bone to bone)

Typically, a muscle stretches across a joint. The muscle origin is on the larger bone,
which remains relatively stationary, and its insertion is on the smaller bone, which
moves relative to the larger bone upon contraction. Muscles work in groups.

Agonist is a classification used to describe a muscle that causes some specific movement
to occur. They are the muscles that are primarily responsible for
generating movement!!!

- When an agonist contracts, the antagonist stretches and vice-

versa!!

An antagonist is a classification used to describe a muscle that acts in opposition to the

specific movement generated by the agonist and is responsible for returning a limb to
its initial position.

- Antagonistic muscles are found in pairs called antagonistic pairs.

- These consist of an extensor muscle, which "opens" the joint (i.e. increasing
the angle between the two bones), and a flexor muscle, which does the
opposite to an extensor muscle.

- An example of antagonistic muscles is the upper arm muscles, the biceps

and triceps.

Synergist muscles assist the agonist by stabilizing the origin bone or by

positioning the insertion bone during the movement. In this way, skeletal
muscle allows for movement and posture..

Skeletal muscle allows for:

1) movement
2) posture
3) movement of substance (blood and lymph)
4) generating heat (shivering controlled by the hypothalamus)
A muscle uses leverage by applying a force to a bone at its insertion point and rotating
the bone in some fashion about the joint. This is a likely MCAT topic because it applies
the physics concept of leverage to a biological system. It may seem strange, but most
lever systems of the body typically act to increase the required force of a
muscle contraction. In other words, a greater force than mg is required to lift a mass
m. This is done in order to reduce the bulk of the body and increase the
range of movement. If the muscle has a shorter lever arm, it is closer to
the body, and thus creates less bulk.

Skeletal Muscle Contractions

The smallest functional unit of skeletal muscle is the sarcomere!!

Sarcomeres are highly organized assemblies of two types of filaments – actin

filaments and filaments of muscle-specific myosin – II.

- The thick filament system is composed of myosin protein which is connected

from the M-line to the Z-disc It also contains myosin-binding protein C
which binds at one end to the thick filament and the other to Actin. These
thick filaments are centrally positioned in each sarcomere!!

- The thin filaments are assembled by actin monomers. Which also involves
tropomyosin and troponin (Ca2+ binds here); a dimer which coils itself
around the F-actin core of the thin filament.

a) The thin filaments are attached by their plus ends to

a structure known as the Z disc!!

2) Nebulin (associated with the thin filament) and Titin (associated with the
thick filament) gives stability and structure to the sarcomere.

3) Neither actin nor myosin changes its length during a muscular

contraction; instead the proportion of myosin and actin
overlap increases!!!

Sarcomeres are positioned end to end to form myofibrils!!

Note: Myofibrils are the contractile elements of the muscle cells!!

Each myofibril is surrounded by the sarcoplasmic reticulum, which is a special type of

smooth ER.
 - The lumen of the sarcoplasmic reticulum is filled with Ca +2 ions!!

Lodged between the myofibrils are mitochondria and many nuclei.

- Skeletal muscle is multinucleate (many nuclei)!!!

A modified membrane called the sarcolemma warps several myofibrils together to

form a muscle cell or muscle fiber.

Many muscle fibers are further bound into a fasciculus, and many fasciculae make up a
single muscle.

A muscle contraction begins with an action potential. A neuron attaches to a

muscle cell forming a neuromuscular synapse!!

Recall: The neurotransmitter, acetylcholine, is used by:

 - Somatic transmission
- preganglionic neurons in both ANS systems
- Postganglionic neurons in the parasympathetic
- Cholinergic receptors
a) Two types of cholinergic receptors:

1) Muscarinic receptors are found on the effectors

of the parasympathetic nervous system.
2) Nicotinic receptors are found on the postsynaptic
cells of the synapse between ANS
preganglionic and postganglionic neurons
and on skeletal muscle membranes at the
neuromuscular junction

Recall: chemical synapse (called a motor end plate

when connecting a neuron to a muscle)
is unidirectional

- time between heartbeats is increased with acetylcholine

The action potential of the neuron releases acetylcholine (because this is part of the
somatic nerve system control) into the synaptic cleft. The action potential activates
ion channels in the sarcolemma creating an action potential there. It then moves
deep into the muscle cell via small tunnels call T-tubules.

- Sodium-gated channels open during the depolarization of nerves, while

most muscle cells, including skeletal, cardiac, and smooth, rely on
calcium- gated channels!!!!

A T-tubule (or transverse tubule) is a deep invagination of the sarcolemma, which is

the plasma membrane, only found in skeletal and cardiac muscle cells!! These
invaginations allow depolarization of the membrane to quickly penetrate to the interior of
the cell

- T-tubules allow for a uniform contraction of the muscle by allowing the

action potential to spread through the muscle cell more rapidly!!
The action potential then is transferred to the sarcoplasmic reticulum, which then release
Ca 2+ ions and the 5 stage cycle of muscle contraction begins.

At the end of the 5 stage cycle Ca 2+ ions are actively pumped (requires ATP
and against concentration gradient) back into the sarcoplasmic reticulum!!!

Myosin and actin work together sliding alongside each other to create the contractile
force of skeletal muscle. THEY DON’T CONTRACT/CHANGE THEIR LENGTH
only the portion of which they overlap increases!!!

1) First, tropomyosin covers an active site on the actin preventing the

myosin head, which is cocked in a high-energy position with a
phosphate and ADP attached, from binding

2) Second, in the presence of Ca 2+ ions, troponin pulls the tropomyosin

back exposing the active site and allowing myosin to bind to the actin.

3) Third, the myosin expels the phosphate and ADP and bends to a lower
energy state and dragging the actin along with it (power stroke). This
causes the shortening of the sarcomere and the muscle contraction.
 4) Fourth, ATP attaches to myosin head releasing myosin from actin and
tropomyosin returns and covers active site.

5) ATP splits to phosphate group and ADP and myosin head returns to high
energy position ready to do it again.

Note: As you can see myosin has ATPase activity!!!

Upon muscle contraction, the A-bands (one end of the thick filament to
the other) does not change their length, whereas the I-bands (end of one
thick filament to the other end of an adjacent thick filament) and the H-
bands shorten!!!!

A Motor Unit
The muscle fibers of a single muscle DONT all contract at once!! Instead, from 2-
2000 fibers spread throughout the muscle are innervated by a single neuron.

The neuron and the muscle fibers that it innervates are called a motor unit.

- Most motor units are independent of each other!!

The force of a contracting muscle depends on the # and size of motor units involved
and the frequency of the action potentials.

Typically, smaller motor units are the first to be activated then larger ones,
resulting in a smooth increase in force generated!!

Muscles requiring intricate movements, i.e. The fingers, have smaller motor units
while other muscles requiring great force have large motor units.

Skeletal Muscle Type

There are three (3) types of muscle fibers:

1) Slow oxidative (type I) or slow-twitch fibers

- Are red because of large amounts of myogoblin.

a) myogoblin is an oxygen storing protein similar to hemoglobin
b) it contains only one protein subunit and can store only one oxygen
c) stores oxygen inside muscle cells.

Recall: Myoglobin is a single-chain globular protein, containing a heme (iron-containing

porphyrin) prosthetic group in the center around which the remaining apoprotein
folds. Unlike the blood-borne hemoglobin, to which it is structurally related, this
protein does not exhibit cooperative binding of oxygen. Instead, the
binding of oxygen by myoglobin is unaffected by the oxygen pressure in the
surrounding tissue. Myoglobin is often cited as having an "instant binding
tenacity" to oxygen given its hyperbolic oxygen dissociation curve. High
concentrations of myoglobin in muscle cells allow organisms to hold their breaths
 longer. It is found mainly in muscle tissue where it serves as an intracellular
storage site for oxygen

- Large amounts of mitochondria!!!

- Produce ATP slowly!!
- Slow to fatigue!!
- Slow contraction velocity!!
- Rely on aerobic metabolism!!
- Marathon runners tend to have more type I fibers, generally through a
combination of genetics and training.

2) Fast oxidative (type II A) or fast-twitch A fibers.

- are also red

- produce ATP more quickly!!
- contract rapidly!!
- resistant to fatigue but not as much as Type I fibers
- more likely to produce lactic acid than Type I fibers

3) Fast glycolytic (Type II B) or fast-twitch B fibers.

- Appear white because of low myoglobin content!!

- Contract very rapidly!!!
- Contain large amounts of glycogen!!!
- more likely to produce lactic acid than Type II A fibers

Large amounts of type I fibers are found in the postural muscles. Large amounts
of type II A fibers are found in the upper legs. Large amounts of type II B fibers
are found in the upper arms.

Adult human skeletal muscles DONT generally undergo mitosis to create new
muscle cells, this is because they are so specialized that they have lost the ability to
undergo mitosis!!

Recall: In humans, liver cells spend a great deal of time in G0. Mature
neurons and muscle cells are in G0 permanently . Liver
(hepatic) and pancreatic cells are normally in G0 but can reenter normal
division

Instead through forceful, repetitive contractions changes occur which include: the
diameter of muscle fiber increases, the number of sarcomeres and mitochondria
increases, and sarcomeres lengthen. This is called hypertrophy.

Hypertrophy is the increase in the volume of an organ or tissue due to the

enlargement of its component cells!!!
It should be distinguished from hyperplasia, in which the cells remain approximately
the same size but increase in number!!!

Cardiac Muscle
The human heart is composed mostly of cardiac muscle, which is involuntary.

Recall: The rate of these contractions is controlled by the autonomic

nervous

system but the autonomic nervous system doesn’t initiate the

contractions

Recall: The parasympathetic, vagus nerve innervates the SA node, slowing

down the contractions and increases the digestive activity in the
intestines

Like skeletal muscle, cardiac muscle is striated, which means that it is composed of
sarcomeres!!

However, cardiac muscle cells contain ONLY one nucleus, and are separated
from its neighbor by an intercalated disc!!!

The intercalated discs contain gap junctions which allow an action potential
to spread from one cardiac cell to the next via electrical synapses!!!

The mitochondria of cardiac muscle are larger and more numerous!!!

Cardiac muscle isn’t connected to bone like skeletal muscle!!

Like skeletal muscle it grows via hypertrophy!!

The action potential of cardiac muscle exhibits a plateau after depolarization !!

The plateau is created by slow voltage-gated calcium channels which allow
calcium to enter and hold the inside of the membrane at a positive potential
difference!!

Note: This lengthens the time of contraction!!

A notable difference between skeletal and cardiac myocytes is how each elevates the
myoplasmic Ca2+ to induce contraction. When skeletal muscle is stimulated by somatic
motor axons, influx of Na+ quickly depolarizes the skeletal myocyte and triggers
calcium release from the sarcoplasmic reticulum.

In cardiac myocytes, the release of Ca2+ from the sarcoplasmic reticulum is induced
by Ca2+ influx into the cell through voltage-gated calcium channels on the
sarcolemma. This phenomenon is called calcium-induced calcium release and
increases the myoplasmic free Ca2+ concentration causing muscle contraction.

The voltage-gated calcium channels in the cardiac sarcolemma are generally

triggered by an influx in sodium during the "0" phase of the action potential (see
below).

The cardiac action potential has five phases.

Like skeletal muscle, cardiac muscle grows by hypertrophy.

Smooth Muscle
Smooth muscle is mainly involuntary, and it’s innervated by the autonomic nervous
system (sympathetic and parasympathetic).

Like cardiac muscle, smooth muscle cells contain only ONE nucleus!! Smooth
muscle contractions are usually longer and slower than skeletal muscle contractions.

Smooth muscle tissue differs from both skeletal and cardiac muscle tissues in structure
and function

Actin and myosin are present in all three muscle types!! In skeletal and
cardiac muscle cells, these proteins are organized in sarcomeres, with thin and thick
filaments. The internal organization of a smooth muscle cell is very different:

1) A smooth muscle fiber has no T tubules, and the sarcoplasmic reticulum

forms a loose network throughout the sarcoplasm.

2) Smooth muscle tissue has no myofibrils or sarcomeres (non-striated)!! As

a result, this tissue also has no striations and is called nonstriated muscle.

3) Don’t have troponin!!

4) Thick filaments are scattered throughout the sarcoplasm of a smooth muscle

cell. The myosin proteins are organized differently than in skeletal or cardiac
muscle cells, and smooth muscle cells have more cross-bridges per thick
filament.

5) In addition, smooth muscle cells contain intermediate filaments, which are

attached to dense bodies. The dense bodies and intermediate filaments are
attached to each other, and the thick and thin filaments are attached to the
intermediate filaments, so when sliding occurs between thin and thick
filaments, the cell causes the intermediate filaments to pull the
dense bodies together which shortens the cell length wise!!!

6) Dense bodies are not arranged in straight lines, so when a contraction

occurs, the muscle cell twists like a corkscrew!!

7) Adjacent smooth muscle cells are bound together at dense bodies,

transmitting the contractile forces from cell to cell throughout the
tissue!!!

8) Although smooth muscle cells are surrounded by connective tissue, the

collagen fibers never unite to form tendons as they do in skeletal muscles.

There are two types of smooth muscle:

1) single-unit (also called visceral, is the most common)

 - single unit smooth muscles are connected by gap
junctions spreading the action potential from a single
neuron through a large group of cells, allowing the cells
to contract as a single unit!!!

- So both cardiac and smooth muscle contain gap junctions!!!

- are found in small arteries and veins, the stomach, intestines, uterus,
and urinary bladder

2) multiunit

- Each multiunit smooth muscle fiber is attached directly to a

neuron.

- A group of multiunit smooth muscle fibers can contract

independently of other muscle fibers in the same location!!!

- Found in large arteries, bronchioles, pili muscles attached to hair

follicles and the iris.

In addition to responding to neural stimulus, smooth muscle also contracts or

relaxes in the presence of hormones, or to change in pH, O2, and CO2
levels, temperature and ion concentrations!!

Ex. Epinephrine constricts smooth muscle and dilates skeletal muscle.

Note: All muscles contract to increased cytosolic calcium concentrations!!

Recall: Muscles and the liver store large amounts of glucose!!

Bone
Bone is a living connective tissue.

Its functions are support of soft tissue, protection of internal organs, assistance in
movement of the body, mineral storage, blood cell production and energy storage in
the form of adipose cells in bone marrow.

There are two types of bone:

 1) Mature
a) lamellar bone is mature, strong, with layers of highly organized
parallel collagen fibers

- There are two types of lamellar bone:

I) compact
II) spongy

2) Immature
a) Woven bone is immature, mechanically weak, it is the first bone to
form during development and in fracture repair

Bone tissue contains four types of cells surrounded by an extensive matrix:

1) Osteoprogenitor (osteogenic) cells

- differentiate into osteoblasts and other cells. These are the cells
replaced by a bone marrow transplant

2) Osteoblasts

- secrete collage and organic compounds upon which bone is formed.

- Incapable of performing mitosis
- As osteoblasts release matrix material around themselves, they become
enveloped by the matrix and differentiate into osteocytes.

3) Osteocytes

- exchange nutrients and waste materials with the blood

- incapable of mitosis
- PTH increases osteocyte activity

4) Osteoclasts

- resorb bone matrix, releasing minerals into the blood

- believed to develop from white blood cells called monocytes

Recall: parathyroid hormone (PTH)

- a peptide hormone

- Increases blood calcium by increasing osteocyte

absorption of calcium and phosphate from the bone and
stimulates the proliferation of osteoclasts.
 - Decreases bone density and increases renal (kidney)
calcium reabsorption and renal (kidney) phosphate
excretion

i. vitamin D increases calcium reabsorption in the

intestine (increases blood calcium) and promotes
normal bone formation and mineralization. It is
activated by PTH. This occurs in the kidney

- PTH secretion is regulated by the calcium ion plasma

concentration and parathyroid glands shrink or grow
accordingly.

- If [Ca+2] in the blood is high then PTH secretion will

decrease

Involved in osteoporosis, if high levels are present

Recall: Calcitonin – secreted by the thryoid

- large peptide hormone
- decreases blood calcium by decreasing osteoclast
activity & #
- increases bone density
- calcium levels can be effectively controlled in humans in
the absence of calcitonin

Action of Calcitonin: puts calcium in bones

(decreases serum Ca2+ levels)

Action of Parathyroid Hormone: gets rid of calcium from bones

(increases serum Ca2+ levels)

A typical long bone has a long shaft called the diaphysis and two ends, each composed
of metaphysis and epiphysis.

Recall: testosterone stimulates closure of the epiphyses of the long bones

A sheet of cartilage in the metaphysic called the epiphyseal plate is where long
bones grow in length.
Spongy bone contains red bone marrow and is where hemopoiesis (red blood
cell development) occurs!!

Compact bone surrounds the medullary cavity (which holds yellow bone
marrow)

- Yellow bone marrow contains adipose cells for fat storage!!

- Compact bone is highly organized.

Osteoclasts burrow tunnels, called Haversian (central) canals, through

compact bone!!!

- Haversion canals contain blood and lymph vessels, and are connected
by crossing canals called Volkmann’s canals!!!

The osteoclasts are followed by osteoblasts, which lay down a new matrix
onto the tunnel walls forming concentric rings called lamellae!!

Osteocytes trapped between the lamellae exchange nutrients via canaliculi!!

The entire system of lamellae and Haversian canal is called an osteon (Haversian
system)!!
Calcium salts are only slightly soluble, so most calcium in the blood is not in the form
of free calcium ions, but is bound mainly to proteins and, to a much lesser extent, by
phosphates (HPO4 2-) and other anions.

Too much calcium results in membranes becoming hypoexcitable producing

lethargy, fatigue, and memory loss; too little produces cramps and
convulsions!!

Most of the Ca 2+ in the body is stored in the bone matrix as hydroxyapatite

[Ca5(PO4)3(OH)].
Collagen fibers lie along the lines of tensile force of the bone, giving the bone great
tensile strength.

Hydroxyapatite crystals lie alongside collage fibers, and give the bone greater
compressive strength than the best reinforced concrete.

** The bone acts as a storage site for Ca 2+ and HPO4 2- **

REMEMBER: Bone is the site of ALL blood cell formation and stores energy in the
form of fat. Bone also stores calcium and phosphate, helping to maintain a
consistent concentration of these ions in the blood!!!

Most bones fall into one of four categories:

1) Long  long bones have a shaft that is curved for strength. Composed of
spongy and compact bone. Ex. Leg, arm, finger and toe
bones

2) Short  cuboidal in shape. Ex ankle and wrist bones

3) Flat  made from spongy bone surround by compact bone. Provide large
areas for muscle attachment, and organ protection Ex. Skull,
sternum, ribs and should blades
4) irregular

Cartilage
Cartilage is flexible, resilient connective tissue.

- It is composed primarily of collagen (a peptide), and has great tensile

strength.

- It contains NO blood vessels or nerves except outside in its outside membrane,

called the perichondrium

- It can’t constrict!!

- Receives nutrients via simple diffusion!!

- It is formed by chondrocytes!!

There are three types of cartilage:

1) Hyaline – most common, its reduces friction and absorbs shock in joints

2) Fibrocartilage

3) elastic

Joints
Joints can be classified by structure into three (3) types:

1) Fibrous joints
 - occurs between two bones held closely and tightly together by
fibrous tissue!!
- little or no movement
- i.e. skull and teeth

2) Cartilaginous joints

- occurs between two bones held closely and tightly together by

cartilage!!!
- little or no movement
- i.e. ribs and sternum

3) Synovial joints

- are NOT bound by intervening cartilage!!

- they are separated by a capsule filled with synovial fluid

- the fluid provides lubrication and nourishment to the cartilage

and contains phagocytotic cells!!!

- synovial joints allow for a wide range of movement

Skin

The integumentary system is the organ system that protects the body from damage,
comprising the skin and its appendages (including hair, scales, and nails).

Skin is an organ.

Some important functions of skin are:

1) Thermoregulation

- the skin helps to regulate body temperature

- it can dissipate heat in the form of sweat, but most is in the form of
radiation. Of course radiation, is only effective if the body is higher than
room temperature.
- Blood can also be shunted away from the capillaries of the skin to
reduce heat loss, keeping the body warm.
- Hair can also be erected (piloerection) via sympathetic stimulation
trapping heat in the body from escaping.
- Skin has both warmth and cold receptors.
 2) Protection
- physical barrier to abrasion, bacteria, dehydration, chemicals and UV
radiation

3) Environmental sensory input

- gathers information from the environment by sensing temp, pressure
pain and touch

4) Excretion
- water and salts are excreted through the skin. This water loss occurs by
diffusion through the skin and is independent of sweating.
- Adults lose one quarter to one half liter of water per day via this type of
insensible fluid loss. Burning of the skin can increase this type of
water loss dramatically

5) Immunity
- contains specialized cells (langerhans cells) in the epidermis that are
components of the immune system

6) Blood Reservoir
- vessels in the dermis hold up to 10% of the blood of a resting adult

- Like veins and the liver

7) Vitamin D synthesis

- UV radiation activates a molecule that is a precursor to vitamin D

and is then modified in the liver and kidney to produce vitamin D!!!

The skin has three (3) principal layers:

1) Epidermis

- is avascular (contains no blood vessels) epithelial tissue!!

- It consists of 4 major cell types:

- 90% of the epidermis is composed of Keratinocytes, which

produce the protein keratin that helps water proof the skin

- Melanocytes transfer melanin (skin pigment) to

keratinocytes
 - Langerhans cells interact with the helper T cells of the
immune system

- Merkel cells attach to sensory neurons and function in the

sensation of touch

- There are 5 layers or strata of the epidermis

a) The deepest layer contains Merkel cells and stem cells!! The
stem cells continually divide to produce keratinocytes and other
cells. Keratinocytes are pushed to the top layer. As they rise,
they accumulate keratin and die, losing their cytoplasm, nucleus,
and other organelles.

- Exposure to friction and pressure stimulates the epidermis to thicken and

form a callus

2) Dermis

- is connective tissue derived from mesodermal cells!!

- The dermis is embedded by blood vessels, glands, nerves, and hair
follicles
- Collagen in the dermis provides the skin with strength and elasticity
- It is thick in the palms and soles.

3) Subcutaneous layer (hypodermis / superficial fascia)

- contains fat which is an important heat insulator for the body.
Hair is a column of keratinized cells held tightly together. As new cells are added
to its base, the hair grows. Most hairs are associated with a sebaceous (oil) gland
that empties oil directly into the follicle and onto the skin. When contracted,
smooth muscle (arrector pili), also associated with each hair stands hair up
pointing it perpendicular to the skin. Nails are also keratinized cells.
Sudoriferous (sweat) glands are found in the skin separate from hair follicles.
Ceruminous glands produce a wax-like material found in the ears.