THE INTEGUMENTARY SYSTEM

The skin or cutis covers the entire outer surface of the body. Structurally, the
skin consists of two layers which differ in function, histological appearance
and their embryological origin. The outer layer or epidermis is formed by an
epithelium and is of ectodermal origin. The underlying thicker layer,
the dermis, consists of connective tissue and develops from the mesoderm.
Beneath the two layers we find a subcutaneous layer of loose connective
tissue or hypodermis, which binds the skin to underlying structures. Hair,
nails and sweat and sebaceous glands are of epithelial origin and collectively
called the appendages of the skin.

The skin and its appendages together are called the integumentary system.

sections of skin - H&E, trichrome or van Gieson

Skin, thick - H&E, trichrome

A good starting point is to identify the
main layers (epidermis, dermis and
hypodermis) of the skin at low
magnification.
The three layers forming the skin can
be identified in all skin sections. The
epithelium forming the surface layer,
the epidermis, is usually the darkest
layer visible. Sublayers are visible in
the epidermis. Their staining varies -
not just between stains but also
between different H&E stained
preparations (possibly depending on
tissue preservation and how fresh the
staining solutions were). At the
transition from the epidermis to the
dermis, staining will become lighter.
The lighter stained layer, the dermis,

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consists of dense irregular connective tissue. The dermis is much thicker
than the epidermis. In thick skin, dermal papillae create a very irregular
border between epidermis and dermis. The hypodermis is the lightest layer
visible and consists mainly of adipose tissue. Dense connective tissue
strands may extend from the dermis deep into the hypodermis and anchor
the skin to underlying structures.

The Epidermis

The epidermis is a keratinised stratified squamous epithelium. The main

function of the epidermis is to protect the body from harmful influences from
the environment and against fluid loss. Five structurally different layers can
be identified:

The stratum basale

is the deepest layer of the epidermis (closest to the dermis). It consists of a
single layer of columnar or cuboidal cells which rest on the basement
membrane. Basal cells are the stem cells of the epidermis. Their mitotic
activity replenishes the cells in more superficial layers as these are
eventually shed from the epidermis.
The renewal of the epidermis takes about 3 to 4 weeks in humans.

In the stratum spinosum,

the cells become irregularly polygonal.
The cells are often separated by
narrow, translucent clefts. These clefts
are spanned by spine-like
cytoplasmatic extensions of the cells
(hence the name of the layer and of its
cells: spinous cells), which
interconnect the cells of this layer.
Spines of cells meet end-to-end or
side-to-side and are attached to each other by desmosomes. In addition to
the usual organelles of cells, EM shows membrane-bound lamellar
granules in the cytoplasm of the spinous cells.

The stratum granulosum

consists, in thick skin, of a few layers of flattened cells. Only one layer may
be visible in thin skin. The cytoplasm of the cells contains numerous fine

2
grains, keratohyalin granules. The keratohyalin is not located in membrane-
bound organelles but forms "free" accumulations in the cytoplasm of the
cells. The cells begin to release the contents of the lamellar granules. The
lipids contained in the granules come to fill the entire interstitial space,
which is important for the function of the epidermis as a barrier towards the
external environment.

The stratum lucidum

consists of several layers of flattened dead cells. Nuclei already begin to
degenerate in the outer part of the stratum granulosum. In the stratum
lucidum, faint nuclear outlines are visible in only a few of the cells. The
stratum lucidum can usually not be identified in thin skin.

In the stratum corneum,

cells are completely filled with keratin filaments (horny cells) which are
embedded in a dense matrix of proteins. Individual cells are difficult to
observe because (1) nuclei can no longer be identified, (2) the cells are very
flat and (3) the space between the cells has been filled with lipids, which
cement the cells together into a continuous membrane. In the EM, the cell
membranes appear thickened and interdigitate with those of neighbouring
cells. Closest to the surface of the epidermis, the stratum corneum
somewhat looser appearance. Horny cells are constantly shed from this part
of the stratum corneum.
The protection of the body by the epidermis is essentially due to the
functional features of the stratum corneum.

Variations in the thickness of the epidermis (~0.1 mm in thin skin, 1 mm or

more in thick skin) are mainly the result of variations in the thickness of the
stratum corneum, although the other layers also vary in thickness. Cells of
the epidermis of the skin will at some time of their life keratinise and are
collectively also called keratinocytes.

Keratinisation should not be used as a synonym for the formation of the

stratum corneum: other stratified squamous epithelia may become
keratinised but may not form a stratum corneum in which cells join to form a
horny cell membrane.

sections of skin - H&E, trichrome or van Gieson

Skin, thin - H&E and Skin, thick, trichrome

The most superficial part of the epidermis is formed by the stratum corneum.
3
Nuclei are not visible in this layer. Cell outlines may be visible at high
magnification or, in the form of artefacts, as cracks or clefts in the stratum
corneum. The stratum granulosum is formed by a single layer of very dark
and flattened cells in thin skin. Several layers of cells containing keratohyalin
granules are visible in thick skin. Polyhedral cells with clear outlines form the
stratum spinosum. The stratum basale is formed by a single layer of cuboidal
or columnar cells and delimits the epidermis from the dermis.
At high magnification, the basal cytoplasm of the basal cells seem to
interdigitate with the underlying dermis. Similar to the dermal papilla, this
irregular border at the cellular level, the dermal-epidermal junction, anchors
individual basal cells firmly to the underlying dermis.
Identify and draw the epithelium in thick and thin skin. Identify in your
drawing as many of the layers of the epidermis as possible.

Other Cells of the Epidermis

The red and yellow hues of the skin are due to haemoglobin in the red blood
cells, which pass through the capillaries beneath the epidermis, and
carotene, which accumulates in fat cells found in the dermis and
hypodermis.

Melanocytes

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The brown colour component is due to melanin, which is produced in the skin
itself in cells called melanocytes (typically 1000-2000 / sqr. mm). These cells
are located in the epidermis and send fine processes between the other
cells. In the melanocytes, the melanin is located in membrane-bound
organelles called melanosomes. The cell bodies of melanocytes are difficult
to distinguish in ordinary LM preparations, because the melanosomes are
located mainly in the processes of the cells.

Melanocytes can transfer melanin to

keratinocytes - mainly to the basal
cells. The fine processes of
melanocytes may invade
keratinocytes and bud-off part of the
melanocyte-cytoplasm, including the
melanosomes, within the
keratinocytes. Melanin protects the
chromosomes of mitotically active
basal cells against light-induced
damage.

Pigmentation is not just under the control of light. Hormones produced by

the pituitary and the adrenal glands also affect pigmentation. Diseases of
these two endocrine organs often result in changes of pigmentation of the
skin.

Although melanocytes are also ectodermal in origin, they are derived

exclusively from the neural crest of the embryo, from where they migrate to
all other parts of the body.

Langerhans Cells

are another cell type found within the epidermis. Morphologically they are
not unlike melanocytes, but functionally they are more closely related to
macrophages. They are important in immune reactions of the epidermis.
Their fine processes form a network between the cells of the epidermis and
phagocytose antigens which have entered the epidermis. Langerhans cells
may only be temporary residents of the skin. If they have come into contact
with an antigen, they can migrate to regional lymph nodes, where they
initiate an immune response.

T-lymphocytes

5
are, like Langerhans cells, a group of cells functioning in the immune system.
Some of them will be present in the epidermis. Together with Langerhans
cells they are sometimes referred to asSALT, i.e. skin-
associated lymphoid tissue.

The Dermis

The dermis is the thick layer of connective tissue to which the epidermis is
attached. Its deepest part continues into the subcutaneous tissue without a
sharply defined boundary. Its thickness is for this reason difficult to
determine but 1-2 mm is a good guestimate for "average" skin. The dermis
may be divided into two sublayers (again without a sharp boundary):

The papillary layer consists of loose, comparatively cell-rich connective

tissue, which fills the hollows at the deep surface (dermal papillae) of the
epidermis. Capillaries are frequent. Collagen fibres appear finer than in the
reticular layer.

The reticular layer appears denser and contains fewer cells. Thick collagen
fibres (5-10 µm) often aggregate into bundles (up to 100 µm thick). The
fibres form an interlacing network, although their predominant direction is
parallel to the surface of the skin. A preferred orientation of the collagen
fibres is not visible in the sections, but the main orientation of the fibres
differs in skin from different parts of the body. Usually, their main orientation
will follow the "lines of greatest tension" in the skin (Kraissl lines). This is of
some surgical importance since incisions parallel to these lines will heal
faster and with less formation of scar tissue.

Kraissl lines have been defined in living humans. They not always coincide
with the cleavage lines, which Langer defined (Langer's cleavage lines)
about a century before Kraissl in cadavers.

Elastic fibres are found in both the papillary (fine fibres) and reticular (coarse
fibres) layers.
They can not be identified in H&E stained sections.

6
sections of skin - H&E, van Gieson
Van Gieson stained sections are particularly nice if the van Gieson stain has
been combined with an elastin stain.

Skin, thin - H&E and Skin, thick - van Gieson & elastin
How easy it is to differentiate between the papillary and reticular layer of the
dermis depends on the preparation - you may have to look at several
preparations. Immediately beneath the epidermis you should see a layer
which at low magnification appears rather evenly stained. At high
magnification the stain should resolve into a fine network of collagen fibres,
which blend with equally fine elastic fibres. Cells are more numerous in the
papillary layer and you should see more nuclei in this area than in the
deeper reticular layer. Also, the papillary layer contains the capillary network
which supplies the epidermis, The reticular layer contains coarse collagen
and elastic fibres and the larger vessels which feed into the capillary network
of the papillary layer..

Draw part of the epidermis and the underlying dermis. Label the layers of the
dermis and structures contained within them.

Appendages of the Skin

7
Hair

A characteristic feature of the human skin is the apparent lack of hair (pili)
on most of the body surface. This is actually not quite true. Most of the skin
is haired although the hair in most areas is short, fine and only lightly
pigmented. This type of hair is called vellus hair.

Truly hairless are only the palms of hands and soles of feet, the distal
phalanges and sides of fingers and toes and parts of the external genitalia.

In those parts of the skin which we perceive as "hairy" we find terminal hairs.
The free part of each hair is called the shaft. The root of each hair is
anchored in a tubular invagination of the epidermis, the hair follicle, which
extends down into the dermis and, usually, a short distance into the
hypodermis. The deepest end of the hair follicle forms an enlargement,
the bulb. Cells in the bulb are mitotically active. Their progeny differentiates
into the cell types which form the hair and the cells that surround its root,
the root sheath. Hair cells keratinise within the lower one-third of the hair
follicle. Above this level it is not possible to identify individual cells within the
hair. Each hair follicle has an associated bundle of smooth muscle,
the arrector pili muscle. This muscle inserts with one end to the papillary
layer of the dermis and with the other end to the dermal sheath of the hair
follicle.

Hair growth is discontinuous. Hairs are lost and replaced by new ones. The
hair follicle goes through different stages that reflect the discontinuous hair
growth. Anagen is the phase of growth. The resting stage is called telogen.
The length of the anagen is variable in different regions of the body - lasting
only a few months for hair of the eyebrows and eyelashes but 2 to 5 years
for hair of the scalp. Hair growth is controlled by a number of hormonal and
hereditary factors and their interactions.

Sections of hairy skin or scalp - H&E

With a few exceptions (thick skin and skin covering parts of the external
genitalia), all skin sections should contain a few hair follicles.

Skin, hairy - H&E

Hair follicles of terminal hair span the entire dermis and usually extend deep
into the hypodermis. Most of them will be cut at odd angles and only a few
good longitudinally or transversely cut profiles are visible. The hair may have
been lost during the preparation of the specimen and not all hair follicles will
contain hairs. Although it is often possible to see the attachment of the

8
arrector pili muscle into the hair follicle or the papillary layer of the dermis,
both attachments are hardly ever visible in the same section.
Draw a hair follicle at low magnification. Try to draw a composite from
several hair follicles and associated structures, which captures their
appearance from the bulb to the epidermis.

Sebaceous Glands

Sebaceous glands empty their secretory product into the upper parts of the
hair follicles. They are therefore found in parts of the skin where hair is
present. The hair follicle and its associated sebaceous gland form
a pilosebaceous unit.

Sebaceous glands are also found in some of the areas where no hair is
present, for example, lips, oral surfaces of the cheeks and external genitalia.

Sebaceous glands are as a rule simple and branched (Remember the

nomenclature of glands!). The secretory portion consists of alveoli. Basal
cells in the outermost layer of the alveolus are flattened. Basal cells are
mitotically active. Some of the new cells will replenish the pool of basal cells,
while the remaining cells are displaced towards the centre of the alveolus as
more cells are generated by the basal cells. The secretory cells will gradullay
9
accumulate lipids and grow in size. Finally their nuclei disintegrate, and the
cells rupture. The resulting secretory product of lipids and the constituents of
the disintegrating cell is a holocrine secretion.

The lipid secretion of the sebaceous glands has no softening effect on the
skin, and it has only very limited antibacterial and antifungoid activity. Its
importance in humans is unclear. Clinically the sebaceous glands are
important in that they are liable to infections (e.g. with the development of
acne).

slides of hairy skin or thin skin - H&E, trichrome, van Gieson

Skin, hairy - trichrome, H&E

Sebaceous glands will be present in all types of skin other than thick skin.
Their numbers should correlate with the number of hair follicles. If your
section does not contain hair follicles you are unlikely to see a good
sebaceous gland. Sebaceous glands are usually embedded in the dermis.
Although they empty into the hair canal of the hair follicle, this point will only
be visible for a few of them because of the thinness of the sections. It should
however be possible to follow the fate of the secretory cells. Deep in the
sebaceous glands cells are smaller with intact nuclei. Cell size increases with
the accumulation of sebum as the cells are gradually displaced towards the
opening of the gland into the hair follicle. The nuclei condense, become
darker and irregularly shaped.
Draw a sebaceous gland. Emphasise the appearance of the secretory cells in
different parts of the gland. If possible include part of the associated hair
follicle.

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Sweat Glands

Two types of sweat glands are present in humans. They are distinguished by
their secretory mechanism into merocrine (~eccrine) sweat
glands and apocrine sweat glands. In addition, they differ in their detailed
histological appearance and in the composition of the sweat they secrete.

Merocrine sweat glands are the only glands of the skin with a clearly defined
biological function. They are of critical importance for the regulation of body
temperature. The skin contains ~3,000,000 sweat gland which are found all
over the body - with the exception of, once again, parts of the external
genitalia.

Sweat glands are simple tubular glands. The secretory tubulus and the initial
part of the excretory duct are coiled into a roughly spherical ball at the
border between the dermis and hypodermis.

The secretory epithelium is cuboidal or low columnar. Two types of cells may
be distinguished: a light type, which secretes the watery eccrine sweat, and
a dark type, which may produce a mucin-like secretion. The cells have
slightly different shapes and, as a result of the different shapes, the
epithelium may appear pseudostratified.

11
A layer of myoepithelial cells is found between the secretory cells of the
epithelium and the basement membrane.

The excretory duct has a stratified cuboidal epithelium (two layers of cells).

The excretory ducts of merocrine sweat glands empty directly onto the
surface of the skin.

Apocrine sweat glands occur in, for example, the axilla. They are stimulated
by sexual hormones and are not fully developed or functional before puberty.
Apocrine sweat is a milky, proteinaceous and odourless secretion. The odour
is a result of bacterial decomposition and is, at least in mammals other than
humans, of importance for sexual attraction.

The histological structure of apocrine sweat glands is similar to that of

merocrine sweat glands, but the lumen of the secretory tubulus is much
larger and the secretory epithelium consists of only one major cell type,
which looks cuboidal or low columnar. Apocrine sweat glands as such are
also much larger than merocrine sweat glands.

The excretory duct of apocrine sweat glands does not open directly onto the
surface of the skin. Instead, the excretory duct empties the sweat into the
upper part of the hair follicle. Apocrine sweat glands are therefore part of the
pilosebaceous unit.

Some texts argue that the apocrine sweat glands use a merocrine or a
combined merocrine / apocrine secretory mechanism.

merocrine sweat glands: sections of thick skin or thin skin - H&E

apocrine sweat glands: sections of skin from the areolae (pigmented skin
surrounding the nipples), the axilla (arm pit) or skin covering the external
genitalia - H&E

Skin, thick - H&E

Scan along the border between dermis and hypodermis and locate a sweat
gland. The secretory tubulus and the initial segment of the duct usually form
a cluster of round or irregularly shaped profiles, which stain darker than the
surrounding connective tissue. The structural preservation of the sweat
glands may vary quite a bit in the different preparations. The different cell
types in the secretory epithelium of merocrine sweat glands are only visible
in well preserved glands. The red rim around the secretory tubulus is formed
by the cytoplasm of myoepithelial cells. Their small, dark nuclei may be

12
visible close to the periphery of the tubulus.
Draw a small schematic illustrating the relative position of the sweat gland in
the skin. Identify and draw the secretory tubulus and excretory duct. Label
as many features as can be identified.

Nipple - H&E
Like merocrine sweat gland, the
secretory tubulus of apocrine sweat
glands will coil close to the border
between the dermis and the
hypodermis. Only one type of
secretory cell is present and the lining
of the secretory tubulus looks more
uniform than that of merocrine sweat
glands. The key feature though is the
very wide lumen of the secretory
tubulus (up to 2 mm). The secretory
cells are surrounded by a layer of
myoepithelial cells. Their cytoplasm
forms the slightly darker outline of the

13
secretory tubulus.
Draw the secretory tubulus of an apocrine seat gland - preferably next to
your drawing of the merocrine sweat gland. Label the structures included in
your drawing.

Muscle Tissue: Histology

Muscle tissue is one of the basic tissue types. Histologically, the muscles of
the body can be classified into 3 types: skeletal, smooth, and cardiac. The 3
types of muscle tissue are based on the morphologic and functional
properties of the cells. One of the defining characteristics of muscle tissue is
its contractility, which generates forces that move the musculoskeletal
system as well as cause movement in the vasculature and multiple organ
systems. This contractility is due to specialized proteins known as
myofilaments, which create organized structures that have the ability to
lengthen and contract.

Definition

Muscle tissue is made up of muscle cells known as myocytes, which is one of

the primary tissue types.

Development

Develops primarily from mesoderm

Intraocular smooth muscles: ectoderm

Myoblasts (embryonic muscle cells): from mesenchyme

Primary characteristics

Contractibility:

Universal muscle cell property

Requires special protein filaments called myofilaments

Myofilaments include actin (thin), myosin(thick), and other proteins

Excitability: responds to stimulus (including electrical, hormonal, and

mechanical)

Extensibility: ability to extend/stretch

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Elasticity: ability to recoil/return to normal shape when tension is released.

Functions

Movement (by exerting a physical force on bone)

Stability:

Support of the skeleton

Stabilize joints

Maintain posture

Control of body passages and openings:

Create the diameter of blood vessels via vasoconstriction and vasodilation

Move food through the GI tract via peristalsis

Sphincters control body openings:

How much light enters the eyes

When food passes through certain parts of the GI tract

Heat production: muscle contraction generates heat.

Types

There are 3 types of muscle tissue based on morphologic and functional

differences:

Skeletal muscles:

Movement of skeleton and other structures (e.g., the eyes)

Long, multinucleated cells with striations

Primarily under voluntary control (though some actions are automatic)

Smooth muscles:

Walls of vessels/hollow organs (e.g., intestines, blood vessels)

Fusiform cells without striations (lack banding pattern)

Slower, involuntary contractions

15
Cardiac muscle/myocardium:

Form most of the walls of the heart

Striated, elongated, branched cells

Under involuntary control

Striated versus non striated muscle

Related to appearance of contractile proteins on microscopy

Striated:

Actin and myosin myofilament proteins are arranged in a regular pattern of

functional units known as sarcomeres.

Skeletal and cardiac muscle

Nonstriated:

Actin and myosin proteins are arranged in an irregular pattern (i.e., they lack
typical sarcomere organization).

Smooth muscle

Skeletal Muscle

General characteristics

Type: striated muscle tissue

Contributes approximately 40% of total human body weight

Over 650 skeletal muscles

Controlled by the somatic nervous system

Primarily voluntary control Gross structure of muscle and surrounding

connective tissue

The muscle is arranged in a hierarchical structure:

Whole muscle:

Made up of multiple muscle fascicles

Surrounded by epimysium:

16
External sheath of connective tissue surrounding the whole muscle

Separates whole muscles from one another

Covered by fascia

Contains collagenfibers, which become continuous with periosteum.

Muscle fascicle:

Bundles of individual muscle fibers

Surrounded by perimysium:

Thin sheaths of connective tissue

Continuous with epimysium at their ends

Muscle fibers:

Individual muscle cells (but typically called “fibers” because they are so long)

Immediately encased by sarcolemma (muscle cell–specific cell membrane)

Surrounded by endomysium:

Thin sheaths of areolar connective tissue

Contain capillaries and nerve fibers to supply each cell/fiber

Continuous with perimysium and epimysium at their ends

Have several hundred to several thousand myofibrils in each muscle fiber

Myofibrils:

Long functional subunits made up of myofilaments within a muscle cell

Surrounded by sarcoplasmic reticulum

Take up a majority of the sarcoplasm

Myofilaments: individual contractile proteins

17
Microscopic structures

General skeletal muscle fiber characteristics:

Multinucleated cells

Nuclei sit on the periphery of the cell.

18
Diameter: 10–100 µm

Sarcolemma:

Muscle cell membrane

Contain transverse (T) tubules:

Channel-like openings that penetrate through the fiber, carrying electrical

signals to all the myofibrils within it.

In close contact with the sarcoplasmic reticulum

Sarcoplasm:

Muscle cell cytoplasm

Primarily filled with protein bundles called myofibrils

Other organelles exist between the myofibrils.

Contains high amounts of:

Myoglobin binds/stores O2 until it is needed

Glycogen: used for energy

Sarcoplasmic reticulum:

Specialized smooth endoplasmic reticulum

Forms a network around each myofibril

Ends dilate into structures called the terminal cisternae, which line the T
tubules

Stores calcium which can be released via gated channels (important during
muscle contraction)

Myofilaments:

Refers to individual proteins that together cause muscle contraction.

Contractile proteins:

Actin: thin myofilaments made of 2 long-coiling protein strands

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Myosin: thick myofilament proteins with a main shaft and a globular head on
each end

Regulatory proteins: regulate binding of actin to myosin

Tropomyosin: blocks the binding sites on actinwhen muscle is relaxed

Troponin: calcium-binding proteins that control contractions

Elastic filament titin: runs through the core of the myosin, emerges from the
end of it, and connects to the Z line

Myofilaments are organized into sarcomeres:

Functional units of striated muscles

Made up of regularrepeating units of interlocking actinand myosinchains

Sarcomeres interlock end to end with each other, forming the long
myofibrils.

Many myofilaments arranged end to end and in parallel make up a myofibril

Microscopic organization: bands seen in striated muscle

The myofibrils are organized in a pattern that creates different bands and
zones when viewed under microscopy. These bands are created by
overlapping actin and myosin strands.

Myosin: thick straight filaments arranged in parallel

Actin:

Thin filaments

Connected to each other at the Z line

Located between each myosin filament

Z band (also called the Z line or Z disc):

Anchors and separates one sarcomere from another

A sarcomere is defined as the region between 2 Z bands.

A (anisotropic) bands:

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Dark bands on microscopy

Formed by entire length of thick myosin filaments, which include

overlapping actinfilaments at the ends

I (isotropic) bands:

Light bands on microscopy

Consist of only thin actin filaments

I bands are between the A bands.

I bands include the Z band.

H zone:

Lighter zone in the middle of the A band

Consists of only myosin filaments → excludes the ends of the myosin that
overlap with actin

M bands:

Fine, dark line in the center of the H zone

Myosin-binding proteins attach here.

Striated muscle: gets its name from the ordered appearance of these bands
on microscopy, which look like stripes

21
22
Types of skeletal muscle fibers

There are 3 primary types of skeletal muscle fibers, found in different

muscles throughout the body based on their function.

Type I fibers: slow-twitch muscles:

Slow oxidative fibers

Fatigue-resistant motor units

Small red fibers

Example: back muscles used to maintain posture

Type II fibers: fast-twitch muscles:

Type IIA:

Fast oxidative, glycolytic fibers

23
Fatigue-resistant

Intermediate/medium size

Used in movement that requires high sustained power

Type IIB:

Fast glycolytic fibers

Store large amounts of glycogen

Fatigue-prone due to buildup of lactic acid during use

Large pink fibers

Motor innervation of skeletal muscle fiber: the neuromuscular

junctionSkeletal muscle cell contraction requires stimulation by an action
potential from motor neurons.

Neuromuscular junction(also called an end plate):

Synapsebetween skeletal muscle cell and motorneuron

Each skeletal muscle cell (fiber) has 1 neuromuscular junction around the
midpoint of cell.

Synaptic knob: a swelling at the end of the motor neuron

Motorend plate: depressions in the sarcolemma in close association with the

synaptic knob

Synaptic cleft: the space between the synaptic knob and the motor end plate

Acetylcholine is released from synaptic vesicles in the synaptic knob →

activates receptors on the motor end plate

Motorunit:

A group of muscle fibers working together that are controlled by a

single motor neuron

Small motor units:

Only a few muscle fibers per neuron

Allow for fine muscle control

24
Large motor units:

Up to several hundred muscle fibers innervated by a single neuron

Used in large postural muscles

Muscle insertion into bone

Muscles attach to bonevia tendons.

Tendons are formed from the 3 connective tissue layers surrounding the
muscles:

Epimysium

Perimysium

Endomysium

Additional connective tissue for added strength

Tendons become continuous with the periosteum of bone

Force generated by the muscle cells is transferred to the

surrounding connective tissue → tendon → bone (generating movement)

Gross organizational patterns of skeletal muscles

There are several different types of organizational patterns based on the

arrangement of bundles the muscle fascicles:

Fusiform: thick in the middle and tapered at each end (e.g., biceps brachii)

Parallel: uniform width of parallel fascicles running along the long axis of a
muscle (e.g., rectus abdominis)

Convergent: fan-shaped, having a broad origin inserting with a single tendon

(e.g., pectoralis major)

Pennate: feather-shaped, having shorter fascicles attaching to a central

tendon at an oblique angle

Unipennate: fascicles all approach the tendon from the same side
(e.g., extensor digitorum)

25
Bipennate: fascicles approach the tendon from both sides (e.g., rectus
femoris)

Multipennate: shaped like a bunch of feathers approaching a single tendon

(e.g., deltoid)

Circular: sphincter or orbicular muscles (e.g., pyloric sphincter in

the stomach, orbicularis oculi of the eyelids)

Comparison of Skeletal, Smooth, and Cardiac Muscle Tissue

Table: Characteristics of muscle types

Type Location Striated versus Motor end plates Characteristics

nonstriated of cells

Skelet Skeletal Striated Present Long,

al muscles cylindrical

Multinucleated

Smoot Walls of Nonstriated Absent Shorter,

h hollow tapered cells
organs
Single central
Blood nucleus
vessels

Cardia Wall of heart Striated Absent (connected Branching

c via intercalated networks
discs)
Single central
nucleus

Clinical Relevance

Myositis: inflammation of muscle tissue. Myositis is generally secondary to

26
infections or inflammatory disorders.

Polymyositis: autoimmune inflammatory myopathy caused by T-cell–

mediated muscle injury. The etiology is unclear, but there are several
genetic and environmental associations.

Polymyositisis most commonly seen in middle-aged women and rarely

affects children. Presentation is with progressive, symmetric, proximal
muscle weakness and constitutional symptoms. Complications may arise
from respiratory, cardiac, or GI involvement.

Rhabdomyolysis: characterized by muscle necrosis and the release of Toxic

intracellular contents, especially myoglobin, into the circulation
Rhabdomyolysis can result from trauma or direct muscle injuries; however,
nonexertional and nontraumatic etiologies (e.g., heatstroke, immobilization,
medication side effects) can also lead to muscle breakdown. The classic triad
of symptoms includes myalgia, weakness, and tea-colored urine, but the
presentation can be nonspecific.

Compartment syndrome: condition that occurs when increased pressure in

a closed muscle compartment exceeds the pressure required to perfuse the
compartment, resulting in muscle and nerve ischemia. Compartment
syndromeis often caused by trauma, such as long-bone fractures, crush
injuries, and burns, but it can also be caused by nontraumatic etiologies,
such as intense muscle activity, group A streptococcal infections, and too-
tight casts.

Myasthenia gravis: autoimmune disorder caused by antibodies against

postsynaptic acetylcholine receptors at the neuromuscular junction. The
disorder can affect ocular, bulbar, extremity and respiratory muscles,
causing weakness and fatigue that fluctuates throughout the day.

Duchenne \muscular dystrophy (DMD): X-linked recessive genetic disorder

that is caused by a mutation in the DMD gene. This mutation leads to
production of abnormal dystrophin, resulting in muscle fiber destruction and
replacement with fatty or fibrous tissue. Affected boys present with
progressive proximal muscle weakness that leads to the eventual loss of
ambulation, contractures, scoliosis, cardiomyopathy, and respiratory failure.

Myocardial infarction: Ischemia and death of an area of myocardial tissue

due to insufficient blood flow and oxygenation, usually from thrombus
formation on a ruptured atherosclerotic plaque in the epicardial arteries.

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Clinical presentation is most commonly with chest pain, but women and
individuals with diabetes may have atypical symptoms.

Cardiomyopathies: group of myocardial diseases associated with structural

changes of the heart muscles (myocardium) and impaired systolic and/or
diastolic function, in the absence of other heart disorders (such as

coronary artery disease or hypertension). The list of causes is extensive,

ranging from familial disorders to underlying diseases and infections.
Symptoms include chest pain, dyspnea, palpitations, and syncope. Some
individuals may be asymptomatic and/or present with sudden cardiac death

Uterine Leiomyoma and leiomyosarcomas: Uterine leiomyomas (or uterine

fibroids) are benign tumors arising from smooth muscle cells in the uterine
myometrium. Leiomyosarcomas are malignant tumors, arising de novo (not
from fibroids). Both conditions present with abnormal bleeding, pelvic pain,
and/or bulk symptoms. Fibroids are identified as a hypoechoic, well-
circumscribed, round masses on pelvic ultrasound. Leiomyosarcomas are
usually only diagnosed on a postoperative specimen.

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