Pathophysiology of Muscle, Tendon, and Ligament Injuries

Limb buds occur as early as the fourth week of
development and consist of a core of mesenchyme covered by the apical
ectodermal ridge. During limb bud growth, the proliferating mesenchyme
gives rise to all of the skeletal rudiments. Myotome cells from the
adjacent somites advance into the limb buds and give rise to the
skeletal muscles. By the seventh week, distinct muscle formation has
reached to the level of the hand and foot. The lower five cervical and
first thoracic myotomes lie opposite the upper limb bud, whereas the
second through fifth lumbar and upper three sacral myotomes lie
opposite the lower limb bud. Branches of the spinal nerves that supply
these myotomes reach the base of the limb bud and, as the bud elongates
to form a true limb, the nerves grow into it.

After two months of development, establishment of
neurocontacts with the developing skeletal muscle fibers will occur.
This is critical for muscular development, with complete
differentiation and function of the muscle fibers. Large motor neurons
contact the developing motor fibers of the growing muscles and
establish formation of the neuromuscular junctions. Voluntary control
of skeletal muscle contraction is completed when myelination of the
nerve fibers of the corticospinal tract is complete. Each muscle fiber
is innervated by one nerve ending.

Approximately 40% to 45% of the human body is composed
of skeletal muscle. Skeletal muscle is a highly organized structure
that is surrounded by well-defined fascial layers (Fig. 1-1).
The individual muscle is surrounded completely by a fascial layer
called the epimysium. From the epimysium, extensions of the surrounding
fascia (perimysium) divide the muscle belly itself into multiple
fascicles. Finally, each fascicle is further subdivided into individual
muscle fibers by the endomysium. The muscle fiber is the basic
structural element of skeletal muscle. Skeletal muscle fibers range in
size from 10 to 80 µm in diameter. Each muscle fiber is surrounded by a
plasma membrane known as the sarcolemma. Immediately beneath the
sarcolemma, along the periphery of the muscle fiber, are numerous cell
nuclei. There can be several hundred nuclei for each centimeter of
fiber length. Satellite cells lie along the surface of the muscle and
are thought to be stem cells capable of regenerating muscle tissue in
the event of injury. Individual fibers are made up of smaller subunits
called myofibrils running the length of the muscle. At the end of the
muscle fiber cell, membranes and collagen tissue collect into bundles
to form muscle tendons. Muscle fibers are arranged either parallel or
oblique to the long axis of the muscle. Oblique arrangements are
commonly described as pennate, bipennate, multipennate, or fusiform.

Each muscle fiber is composed of hundreds to several
thousand longitudinally oriented myofibrils. Myofibrils are composed of
thick and thin protein filaments. The thick filaments (myosin) and the
thin filaments (actin) provide the mechanical force during a muscle
contraction by sliding past one another. In addition to myosin, the
thick filaments are also made up of C-protein, M-protein, and titin.
The thin filaments are anchored at one end by a protein structure
called the Z-band, which is oriented at right angles to the filaments.
These Z-bands occur at regular intervals along the length of the
myofibrils and give skeletal muscle its striated appearance.

The sarcomere is the section of the myofibrils between two adjacent Z-bands (Fig. 1-2).
Therefore, myofibrils are constructed of many sarcomeres linked end to
end. Understanding the structure and function of the sarcomere is
important because it is the basic unit of contraction. The sarcomere
can be further divided into an A-band, which is a subunit containing
the critical interdigitation of actin and

myosin
filaments. In the middle of this A-band is the M-band, representing the
middle portion of the thick filaments only. Another section, called the
I-band, is made up of only actin; it does not interdigitate with the
myosin molecules and therefore overlaps two successive sarcomeres where
the actin molecules are anchored to the Z-bands. In the normal resting
state, the thin filaments of the sarcomere are attached at either end
to the Z-band and point toward one another. However, they do not touch
or overlap. This creates a region in the middle of the sarcomere where
the thick filaments are not overlapped by the thin filaments. This is
called the H-zone.

The thick filaments are primarily composed of large
proteins called myosin. On electron microscopic examination, these
molecules look like long rods with two paddles attached at one end.
These paddles are critical in forming the cross bridges between the
thick and thin filaments. In a relaxed muscle, the paddles point toward
the Z-bands. The actin in its normal state resides in the form of a
double helix. Along the notches between the strands of actin are
molecules of troponin and tropomyosin. These proteins enable calcium to
regulate the contraction-relaxation cycle.

Elongation and growth of the muscle occur in both the
muscle fibers and their associated tendons. Sarcomere length remains
fixed throughout development. Additional sarcomeres are added to the
muscle fibers to achieve longitudinal growth in the region of the
musculotendinous junction.

Peripheral nerves enter skeletal muscle at the motor
point. From there, the nerve cell axon branches many times. Skeletal
muscle fibers are innervated by neurons entering the

muscle
in a region called the endplate zone. The cell bodies of these neurons
are located in the anterior horn of the spinal cord. Each motor neuron
branches several times within the muscle and innervates a variable
number of muscle fibers. However, each muscle fiber can be innervated
by only one motor neuron. The motor unit is composed of a single motor
neuron and all the muscle fibers it innervates. Muscle fiber type is
related to its interaction with the singular motor nerve, as all muscle
fibers in a single motor unit have the same metabolic and contractile
properties (Fig. 1-3).
The strength of a muscle contraction depends on the number of muscle
fibers that are activated at the same time. As each motor neuron
branches several times and innervates many muscle fibers, the central
nervous system cannot activate a single muscle fiber, but most work
through individual motor neurons in the activation of multiple muscle
fibers comprising the motor unit. Therefore, the degree of control that
is exerted on the strength of the muscle contraction in part depends on
the number of muscle fibers comprising each motor unit that are
activated. Powerful extremity muscles may contain more than 1,000
muscle fibers in each motor unit, whereas when fine control is
required, the motor units may contain only a few muscle fibers. Smaller
motor neurons usually innervate fewer muscle fibers and therefore have
smaller motor units. Often, these neurons are activated first. If more
power is needed, larger motor units are progressively recruited. This
has been referred to as the size principle of motor control.

Different types of motor units—based on structural,
metabolic, and functional variations—have been identified. Different
classification schemes have been proposed. Muscles are able to function
for a short time without oxygen by using the glycolytic pathway to
generate adenosine triphosphate (ATP). Muscle fibers that generate high
power over a short time have been called “fast-twitch,” “white,” or
type II and make extensive use of this pathway. These muscle fibers
release energy rapidly from ATP but regenerate energy stores slowly.
Therefore, these muscles become easily fatigued. Fast-twitch motor
units are generally larger and generate more strength. They have higher
enzymatic activity for the phosphagen and glycolytic systems and are
used predominantly during activities dependent on anaerobic energy.
Type II motor units can be further subdivided. Most commonly, two main
subgroups are considered. Type IIB motor units (or fast glycolytic
motor units) have the fastest contraction time and are the least
resistant to fatigue. This motor unit has the largest number of muscle
fibers, the largest axon, and the largest cell body. Type IIA motor
units are considered to be in between type I and type IIB groups.
Contraction times and fatigue resistance profiles are between type I
and type IIB, as both the oxidative and glycolytic pathways are well
developed. Motor unit size is also intermediate. In contrast, muscle
fibers that are active over a long period of time are considered
“slow-twitch,” “red,” or type I. These fibers are rich in mitochondria
and have a greater oxidative aerobic capacity. Type I motor units are
resistant to fatigue. These motor units are often small and used in
fine manipulations. In addition, they are the first fibers activated
when lower levels of power are required.

Athletes have a special interest in knowing their
distribution of motor unit types. Variations in muscle fiber type
between individuals are common. A preponderance of one type over
another may lead to a greater chance of success in a given sport. For
example, power athletes or sprinters should benefit from higher
concentrations of fast-twitch fibers within their muscles, whereas
distance runners would benefit from having predominantly type I fibers.
It is believed that the distribution of muscle fibers in any one
individual is determined genetically. However, there is evidence for
interconversion between type IIA and type IIB fibers. Certainly, during
training, there is selective recruitment of the appropriate fibers that
are best suited for specific athletic demands.

Motor nerves to the motor unit are generally large,
myelinated fibers. The nerve forms a synapse with the muscle at a
specialized region known as the motor endplate (Fig. 1-4).
Transmission of the impulse is not achieved by direct electrical
transmission but requires a chemical transmission at the motor
endplate. At the end of the neuron, there are fingerlike projections
found between the membranes of the nerve and the muscle. These primary
synaptic folds act to increase the area of membrane interaction between
the nerve and muscle. The nerve terminal is rich in mitochondria and
contains many synaptic vesicles that contain the neurotransmitter
acetylcholine. The presynaptic and postsynaptic membranes are separated
by a small (50 nm) synaptic cleft. In the muscle membrane are
junctional folds containing acetylcholine receptors that mediate the
action of the neurotransmitter and acetylcholinesterase, which acts to
destroy the neurotransmitter.

When the motor neuron is stimulated, electrical impulses
are propagated along the axon toward the neuromuscular junction. When
the action potential arrives at the motor unit, the depolarization
opens up calcium channels in the

axon
terminal. This results in calcium becoming concentrated in the
presynaptic nerve terminal. The sudden increase in the calcium
concentration causes the vesicles to fuse with the terminal axon
membrane and results in the release of acetylcholine into the synaptic
cleft. This acetylcholine passes across this cleft and binds to a
receptor molecule on the postsynaptic membrane. This results in the
opening of channels to permit the influx of sodium ions and the efflux
of potassium ions. The net effect is the depolarization of the muscle
membrane and triggering of the muscle action potential. The
acetylcholine is then rapidly hydrolyzed and deactivated by the enzyme
acetylcholinesterase into choline and acetate. Breakdown products are
then reabsorbed into the terminal axon to be used in the resynthesis of
a new transmitter.

Pharmacologic manipulation of the neuromuscular junction
is possible. Severe muscle weakness in the disease myasthenia gravis is
the result of a shortage of acetylcholine receptors. Inhibition of the
acetylcholinesterase enzyme with neostigmine and edrophonium can allow
the acetylcholine molecules to have a longer life and a better chance
to interact with receptors before they are broken down. Impulse
transmission can be blocked by Curare, which binds to the acetylcholine
receptors. Succinylcholine produces muscle relaxation by keeping the
acetylcholine channels open for too long a period of time. This keeps
the muscle membrane depolarized and refractory to further impulse
initiation.

The muscle action potential is propagated along the
entire length of the muscle fiber. Between the adjacent myofibrils are
elements of the conducting pathway, called the sarcoplasmic
reticulum-transverse tubule system. The T-tubules are internal
extensions of the cell membrane, oriented perpendicular to the long
axis of the cell and bring the action potential into the interior of
the muscle fiber. These often lie at the level of the A- and I-band
junctions. Calcium ions are held in high concentrations in the
sarcoplasmic reticulum. When the adjacent T-tubule system is excited by
a muscle action potential, calcium ions are released into the muscle
cytoplasm and diffuse to the nearby myofibrils. There, they bind
strongly to troponin. This results in structural changes that allow
actin to bind to the myosin cross bridges. This binding elicits a
muscle contraction as ATP is hydrolyzed by myosin and the thick
filaments slide past the thin filaments. The cross-bridging cycle
occurs many times as the thick filaments release from the actin on the
thin filament, return to their original configuration, create another
cross bridge with conformational changes, and further shorten the
muscle fiber (Fig. 1-5). This process may occur
in rapid succession. The thick filaments pull toward each other and
toward the center of the A-band, and the sarcomeres shorten or resist
stretch. During a muscle contraction, the angle between the cross
bridges and the rod portion of the myosin becomes more acute. This has
been described as the sliding filamentswinging cross-bridges theory of
muscle contraction. The sarcoplasmic reticulum contains a calcium pump
that removes the calcium from the myofibrils at the end of a single
contraction. When calcium is no longer available, tropomyosin undergoes
a conformational change, thus preventing further cross-bridge formation.

The tension response by muscle to a single nerve
stimulus is called a muscle twitch. If a second contraction is elicited
before the first one has relaxed, a stronger contraction results. As
the stimulation frequency increases, the tension in the muscle also
increases. When the frequency of activation is high enough, a
continuous contraction (tetanus) will result. Involving more motor
units can also increase the force of muscle contraction. This has been
termed “recruitment.” To increase the overall strength of muscle
contraction, both the frequency of activation and the recruitment of
more motor units are required.

The tension a muscle can generate is also dependent on
the length of that muscle when the contraction begins. The Blix curve
describes this important muscle length-tension relationship (Fig. 1-6). When a muscle is at its normal resting

state and length, there is maximal overlap of the thick and thin
filaments. This maximal overlap allows for the creation of maximum
cross-bridging tension to be developed. Once a muscle is in a
contracted position, the thin actin filaments impede one another. This
interferes with cross bridging and effectively reduces the maximum
tension that can be created. Conversely, stretching the muscle out to a
point where the filaments have minimal cross-bridging contact also
results in a weak muscle contraction. The maximum amount of force
produced by a muscle is proportional to its cross-sectional area. Also,
the total amount and speed of muscle shortening is proportional to the
individual muscle fiber length.

Muscle contraction and function can be studied in
different ways. An isometric contraction (same length) occurs when the
muscle length is held constant and the resultant force is measured. In
an isotonic contraction (same load), the muscle is activated to shorten
against a constant load while muscle length changes with time are
measured. Muscle can also be evaluated under isokinetic activation
(same speed), in which the load accommodates to maintain a constant
velocity of shortening or lengthening. When a muscle is activated,
shortening of the sarcomeres results in force generation. The muscle
will shorten (concentric action) if the resisting load is less than the
force generated by the muscle. Conversely, the muscle will lengthen
(eccentric action) if the resisting force is greater than that
generated by the muscle. Muscles that are stimulated eccentrically can
produce more work than muscles that are activated concentrically. No
motion will occur if the forces are equal.

The force generated by a muscle is transmitted through
the myotendinous junction before integration into the distal tendon.
This is a region of highly folded membranes,which increases the contact
area and decreases stress. In this area, stresses are changed from
tensile to shear. A well-developed basement membrane allows the muscle
force generated to be linked to the collagen fibers of the tendon.
Fibronectin, laminin,and type IV collagen are among the proteins
present in the basement membrane.

ATP is the immediate source of energy needed for muscle
contraction. Once ATP is broken down into adenosine diphosphate
(ADP)/adenosine monophosphate and inorganic phosphate(s) to release
energy,the body must re-create the ATP from one of three available
sources. The most readily available source is creatine phosphate (CP).
When enzymatically broken down,the energy released is used to form ATP
again:

ADP + CP + creatine kinase → ATP + CP

This reaction is primarily used in
high-intensity,short-duration activities such as sprinting,because the
amount of energy available is limited. CP cannot be used directly by
the muscle cells as a source of energy. Some athletes have used oral
creatine supplementation in an attempt to maximize CP levels that may
then promote greater muscle hypertrophy from resistance training.

Anaerobic glycolysis utilizing the hydrolysis of glucose
is the second source of energy. Glucose is metabolized and releases
energy to convert ADP to ATP,as well as forming lactic acid as a
byproduct. Lactic acid buildup causes the symptoms of fatigue. This
inefficient system is a limited source of energy and is used by the
muscle when a lot of energy is needed for a relatively short period of
time.

Aerobic glycolysis occurs when glycogen or triglycerides
are completely broken down to carbon dioxide and water in the presence
of oxygen. This process occurs in the mitochondria of the muscle cells.
It is responsible for releasing the large amounts of energy needed for
ATP resynthesis. A single molecule of glucose can yield 34 molecules of
ATP. This is an excellent energy source for prolonged endurance type of
activities. The amount of oxygen available to the cell is the limiting
factor. Athletes whose diets are rich in carbohydrate have higher
stores of glycogen and therefore may benefit from a higher energy
production (carbohydrate loading). For most individuals,fat storage
provides an abundant source of energy. Breakdown of free fatty acids
can provide sufficient energy to convert large amounts of ADP to ATP.
These fatty acids can be found within the muscle or mobilized from
adipose tissue. It is unlikely that availability is a limiting factor
in energy metabolism.

Although energy metabolism has been broken down into
separate systems,most often, they occur simultaneously to provide
working muscles the energy required for the formation of ATP. The
different motor unit types have varying levels of enzymes required for
both aerobic and anaerobic capacity. The body will emphasize the
appropriate metabolic system based on the intensity and duration of
activity undertaken. This variation has been described as the energy
continuum. For example,brief high-intensity exercise relies on the CP
system. If intensity falls and length of exercise increases,the
anaerobic system is used more to replenish the required ATP. If the
exercise intensity falls further and the length of activity continues
to increase,then the aerobic system becomes most efficient for
supplying energy. The training an athlete performs can significantly
influence which pathways are chosen.

Conditioning has been described as the time it takes for
the body to return to its pre-exercise state after vigorous activity.
The lactic acid must be removed from the muscle, muscle glycogen must
be replenished,phosphagen and ATP must be restored,and the remaining
oxygen debt must be eliminated. Athletes benefit from warming down
after competition because light exercise hastens the removal of the
built-up lactic acid. Lost muscle glycogen can be resynthesized within
a couple of hours after moderate exercise,but it may take as long as 48
hours following prolonged endurance activity. Muscle phosphagen store
replacement occurs rather quickly. Oxygen debt recovery requires
replenishing myoglobin with oxygen in the aerobic recovery of
phosphagen stores,as well as recovery from the oxygen debt needed to
assist the conversion of lactic acid. Conditioning can shorten all
recovery times.

Hormonal manipulation of muscle has become a well-known
concern in the sporting community. Insulin is a hormone secreted by the
pancreas for the regulation of metabolism of food products. This
hormone is considered anabolic because it increases glucose entry into
the muscle cell and increases glycogen synthesis. Amino acid uptake is
increased, resulting in protein synthesis,and protein catabolism is
decreased. These effects are synergistic with growth hormone.
Glucocorticoids oppose these actions by accelerating protein
degradation and increasing the resulting amino acid release. Growth
hormone,a product of the pituitary gland,increases amino acid transport
into the muscle

cell
and stimulates protein synthesis, which results in increased muscle
synthesis. Growth hormone also reduces glucose and protein metabolism
by shifting metabolism toward the use of fatty acids. Synthetic human
growth hormone has led to its increasing use as an anabolic agent.
Testosterone has the main anabolic effect on muscle tissue. It
increases protein synthesis while decreasing the rate of protein
catabolism within the muscle. This results in an increase of the muscle
size, weight, and strength. Another effect of testosterone is the
expression of male sexual characteristics, including increased hair
growth, voice deepening, and genital enlargement. Anabolic steroids
were developed to decrease these “unwanted” characteristics. The
benefit of these compounds to athletes has been to increase strength
with an associated improvement in anaerobic performance. Although
controversy remains in the medical literature on the effectiveness and
safety of these compounds, competing athletes worldwide understand the
possible gains in strength that are possible when used in conjunction
with high-intensity exercise and an appropriate supporting diet.

The embryological study of tendon development must be
still considered to be in its infancy. Relatively little is known about
the embryogenesis of tendons, compared with other musculoskeletal
tissues such as muscle, cartilage, and bone. Tendons, like muscles,
originate from mesoderm. More specifically, they arise from the lateral
plate mesoderm. Although intimately functionally connected when mature,
muscle and tendon are able to develop autonomously. One of the earliest
steps in tendon embryogenesis is the formation of a mesenchymal lamina
along the ectodermal basement membrane. Precursor cells then condense
on the dorsal and ventral sides of this mesenchymal lamina to form the
anlage that will eventually become the flexor and extensor tendons of
the adjacent joints. Interestingly, although tendons are
developmentally autonomous, subsequent muscle-tendon interaction is
required to prevent tendon degeneration. Because tendons attain size
and strength relative to the muscle mass and distance from insertion
during growth and development, it is believed that tenocytes are
responsive to the magnitude and direction of the load. Although the
exact mechanism remains unknown, investigators have shown that isolated
tendon fibroblasts respond to mechanical strains placed upon them. The
role of specific

proteins and the required pattern of expression for normal tendon development are just beginning to be elucidated.

Tendons link the motor units (muscles) to the bones so
that joint motion is possible. They are generally cylindrical in shape
with slight widening and flattening at the musculotendinous junction
and their bony insertion. Notable exceptions are the rotator cuff
tendons and pectoralis muscle tendons, which are flat and platelike at
their insertions.

The predominant cell in tendons is the fibroblast. These
fusiform cells are responsible for the production and maintenance of
collagen and other proteins that confer the flexibility and tensile
strength of tendons. Collagen is by far the largest constituent of
tendons. Almost 90% of the dry weight is accounted for by collagen.
Tendons are primarily composed of type I collagen, but they also
contain small amounts of type III, type IV, type V, and type VI
collagen. The primary structure of collagen is a three-amino acid
residue-repeating pattern. Glycine is present every third amino acid on
average, whereas proline and hydroxyproline each make up 15% of the
molecule.

Proteoglycans are also present with decorin
predominating, but biglycan, lumican, and fibromodulin have also been
detected. Decorin is a sulfate-rich proteoglycan. Studies have shown it
to bind collagen together along the length of fibrils, much in the way
a rubber band holds a bunch of pencils together. It is believed to aid
in the formation of the collagen fibrils. It has been postulated that
decorin regulates fibril diameter, halting further accumulation past a
certain point.

Proteoglycans are thought to regulate collagen fiber
diameter, separate individual fiber bundles, and minimize the shear
stresses fibers experience as they move relative to each other during
normal function. Although tendons function under predominantly tensile
loads, they do experience compressive loads as they pass around
skeletal prominences and pulleys. Some of the pressures experienced in
these regions are substantial, with measurements being reported in the
range of 700 mm Hg. Glycosaminoglycan (specifically aggrecan) content
in these regions is elevated relative to the rest of the tendon. This
is probably a functional adaptation allowing for greater water content
and resultant structural resiliency under compressive conditions.

The metabolic organization through which tendons
maintain and repair themselves is just beginning to be understood.
Although tenocytes initially appear to be spatially distinct within the
matrix of the tendon, like osteocytes, they possess very long processes
that form gap junctions to facilitate communications with other cells
in their locale.

The microarchitecture of a tendon is hierarchical(Fig. 1-7).
Microfibrils make up subfibrils which, in turn, make up fibrils. There
are hundreds of these fibrils within each fascicle. It is these
fascicles that make up the tendon itself. These fascicles are separated
from one another by the endotenon. The endotenon is made of
longitudinally oriented adventitia that is cell-poor. On the surface,
and adherent to the tendon proper, is the epitenon. This diaphanous
layer is composed of fibroblasts one to two cell layers thick.

Ideally, tendons should have tensile strengths far
higher than the maximal forces that the muscles with which they are
contiguous can generate. In addition, they should be able to
accommodate cyclic loading, as well as static loads without diminution
of tensile properties, fatigue, or irreversible elongation. Tendons are
anisotropic structures that demonstrate viscoelastic properties. They
have the highest tensile strength of any soft tissue. There are two
reasons for this fact. Collagen is the strongest fibrous protein in the
body, and the linear arrangement of its fibrils is parallel to the
direction of tensile force, making these structures ideally suited to
resist tension. Strain rate-dependent lengthening is observed. As the
elongation rate is increased, tendons appear stiffer. Because tendons
contain a relatively larger proportion of collagen to ground substance
than other musculoskeletal tissues, they demonstrate less
viscoelasticity and more purely elastic properties than these tissues.
The ultimate tensile strength of human tendons is 50 to 105 MPa.
Elastic strain energy recovery upon unloading of tendons is 90% to 96%
per cycle. The stress strain curve observed for tendons is similar to
those of other soft tissues (Fig. 1-9).

The short toe region results from the straightening of
crimps in the fibrillar structure. This requires relatively small
amounts of force, but because the fibers are already aligned in a
parallel fashion, the region is truncated relative to other
viscoelastic soft tissues. As with other substances, the slope of the
linear region of the curve represents the elastic modulus of the tendon.

Numerous animal models have been used to study the
biomechanical effect of exercise on tendons. Many of the results have
been conflicting. Ultrasonography of human tendon showed that the free
tendon of the vastus lateralis was significantly stiffer in
long-distance runners than in control subjects. A follow-up study
revealed that the knee extensor tendons became stiffer with isometric
training. The mechanism of this increased stiffness does not seem to be
increased collagen concentration, an increase in collagen cross-links,
or hypertrophy of the tendon itself. As alluded to later in this
section, decreased fatigability may be an adaptive response that serves
to prevent catastrophic damage associated with repetitive loading.

Fibrils vary in diameter and, as a function of age,
anatomical site and exercise. Tendons from young animals have
relatively small fibrils that fall within a unimodal distribution. As
animals age, fibril diameters increase and generally segregate in a
bimodal distribution. The stiffness and modulus continue to increase up
until maturity and then levels off. Collagen cross-linking increases
with age. The toe region of the stress-strain curve diminishes because
crimps in the tendon diminish.

Conditions that affect the tendons, as well as the
manifestations of each, are diverse. The mechanisms and pathogenesis of
these injures are also quite different. Tendinopathies may involve the
tenosynovium, the peritenon, the tendon itself, or a combination of
these structures. The initial condition may be inflammation of the
peritenon secondary to overuse. If this inflammation becomes chronic,
the tendon proper may become inflamed or hypovascular as a result of
reduced perfusion through the peritenon. This induces degenerative
changes in the tendon. The mechanism of injury has a direct impact on
how these structures heal. Three main mechanisms of tendon injury are
laceration, contusion, and tensile overload. Tensile overload may
result in midsubstance tears, tears at the musculotendinous junction,
avulsion from bone, or avulsion fracture of the bone at the insertion
site.

One way in which these pathologies may be organized is
by the acuity of their onset. Lacerations, contusions, tears, and
avulsion from bone are the most sudden in their acuity. Although the
treatment of these injuries may be similar, the reasons for their
occurrence are quite different. Because most tendons can handle tensile
forces greater than their accompanying muscles can generate, and
greater than the sheer forces able to be withstood by the bones into
which they anchor, midsubstance tears are uncommon. Musculotendinous
junction tears or avulsion fractures are more common than midsubstance
tendon injuries. Midsubstance tears of tendons require preexisting
tendinopathy at or near the site of the tear. Failure that occurs only
in collagenous material is due to the pulling apart of adjacent
collagen molecules, not the breakage of tropocollagen molecules.
Although within-the-hand and distal upper extremity lacerations
constitute the majority of tendon injuries, degenerative-type injuries
are more common in other anatomical locations.

Less acute in their onset are tendonitis, tendinosis,
and enthesopathies. Tendonitis most commonly occurs as a result of
overuse and is characterized by macroscopic or microscopic injury to
collagen fibrils, tendon matrix, and the supporting microvasculature
that results in inflammation and, secondarily, pain. Overuse tendon
injuries account for a significant percentage of sports injuries. The
ability to repair itself continually may be most important in
preventing tendon overuse injuries. In simulating an in vivo loading
pattern of the extensor digitorum longus tendon of the foot, the tendon
was loaded to 20% of its failure stress. After the equivalent of 4
months of normal walking (approximately 300,000 cycles), the tendon
failed. Because such tendon failure is not observed in vivo, repair and
remodeling must be central to physiological maintenance of the tendon.
It is enticing to speculate that overuse injuries of tendons may be due
to reparative mechanisms that are not able to counterbalance the
microtrauma associated with the inciting activity.

The histological appearance of tendonitis
has been described as angiofibroblastic hyperplasia. The inflammatory
cells present are not characteristic of other acute inflammatory
conditions. Enthesopathies are defined as diseases that occur at the site of insertion of muscle tendons and ligaments into bone or joint capsules. Tendinoses are chronic degenerative conditions of tendons. More specific than chronic degeneration, tendinosis
refers to intrasubstance degeneration without histologic or clinical
signs of inflammation within the tendon. The morphologic changes
evident in tendinosis include proliferation of fibroblasts, appearance
of new capillary tufts, a decrease in collagen fibril diameter, and a
more wavy orientation of the collagen fibers. Matrix components also
show histologic changes. At the gross level, tendinosis shows
thickened, condensed, and desiccated-appearing regions.

Histologically, tendinosis is characterized by
interstitial microscopic failure of the tendon substance or central
tissue necrosis with mucoid degeneration. Because inflammation may or
may not be a part of this process, tendinosis may or may not be
associated with symptoms.

Although tendonitis and tendinoses may be secondary to
systemic disease, most cases result from overuse syndromes. These
overuse syndromes all have some component of chronic inflammatory
response that occurs in or around the tissue. A “tendinosis cycle” has
been described in which tendinosis results from changes in the load
experienced by tendons that are not compensated by adaptations of the
cell matrix. Microtears occur through pathologic tendinous tissue and
eventually result in tissue failure if there is not an adequate
healing, reparative, or hypertrophic response.

Ligaments consist of cellular, extracellular matrix, and
aqueous components. Cell types are fibroblasts, endothelial cells, and
nerve cells. Fibroblasts are the primary cells in ligaments and are
responsible for synthesizing extracellular matrix components, including
collagen. The extracellular matrix is composed of 60% water and 40%
collagens, elastin, proteoglycans, and noncollagenous proteins.
Collagens are fibrillar proteins with high tensile strength composed of
three polypeptide chains arranged in a helical pattern (tropocollagen)
and covalently cross-linked together. Different combinations of
polypeptide chains yield different types of collagen and higher levels
of cross-linking between tropocollagen chains confers greater
mechanical strength to the collagen and ligament. Collagen constitutes
70% to 80% of ligament dry weight. More than 90% of collagen found in
ligaments is type I, approximately 10% is type III, and other types may
be present in smaller concentrations. Ligaments contain a lower
percentage of collagen than tendons. Elastin, a protein rich in glycine
and proline, comprises less than 5% of dry weight in most ligaments. It
is found in higher concentrations in flexible ligaments, such as the
ligamentum flavum. Proteoglycans are composed of polysaccharide chains
[glycosaminoglycans (GAGs)], which are connected to a protein core.
They are negatively charged molecules that bind water and other
positively charged ions. They form less than 1% of ligament dry weight.
Most ligaments have higher GAG content than tendons. Two types of
proteoglycans are found in ligaments: larger molecules with chondroitin
and keratin sulfate GAG chains, and smaller molecules with dermatan
sulfate chains. Proteoglycans serve to maintain ligament water content,
organize the

extracellular
matrix, and interact with cellular elements. Noncollagenous proteins
include fibronectin, a protein that allows cells to interact with the
extracellular matrix.

Ligaments are relatively avascular, but they do contain
small blood vessels originating at the ligament insertion sites. Cells
contained within the ligament are maintained by this blood supply and
through diffusion from the local aqueous environment. Nerve fibers have
been noted in medial collateral ligament (MCL), and ACL specimens and
are postulated to have proprioceptive, mechanoreceptive, and
nociceptive functions.

Structurally, ligaments form cords, strips, and
sheet-like structures that insert into bone on either side of an
articulation. There are intra-articular and extra-articular ligaments.
Their insertions have been described as direct or indirect based how
the collagen fibers attach to bone. Direct insertions, such as the
femoral insertion of the MCL or tibial insertion of the ACL, have
ligament fibers passing directly into the cortex. This transition has
been observed occurring over four zones: ligament, fibrocartilage,
mineralized fibrocartilage, and bone. Indirect insertions, such as the
tibial insertion of the MCL, have a broader area of insertion,
superficial fibers that insert obliquely into the periosteum, and
deeper fibers inserting via Sharpey’s fibers forming the indirect
insertion. Indirect insertions may be elevated off the bone without
cutting the ligament itself, where direct inserting ligaments require
cutting the substance of the ligament to detach it.

Biomechanical properties of ligaments can be described
in terms of the structural properties of the bone ligament bone complex
and mechanical properties of the ligament substance. The structural
properties of the bone ligament bone construct, which are influenced by
ligament composition and insertion type, are tested with tensile stress
and plotted on load-elongation curves. Stiffness is defined as the
resistance of a structure to deformation, or the slope of the
load-elongation curve. This curve has an initial low-stiffness toe
region followed by a higher-stiffness linear region. This increase in
stiffness has been attributed to the initial straightening of the
undulating crimp pattern and nonuniform recruitment of the individual
fibers as represented in the low-stiffness (and larger elongation) toe
region of the curve. As the fiber bundles straighten and more fibers
are recruited, stiffness increases. The ultimate load on the curve is
where construct failure occurs. The slope may decrease before failure
if individual fibers fail before the entire construct fails. Area under
the curve is energy absorbed before failure.

The mechanical properties of the ligament—which are
influenced by collagen composition, collagen fiber orientation, and
interaction with the extracellular matrix—are tested with tensile
stress and plotted on stress-strain curves. This slope of this curve is
the elastic modulus. The tensile strength is the maximum stress before
failure. The elastic modulus of the MCL is approximately twice as much
as the ACL. The MCL has more densely packed fiber bundles per unit area
with less crimp, or wave pattern, and greater fiber diameter than the
ACL. Ligaments also display viscoelastic properties that reflect
interactions of collagen and other extracellular matrix molecules:
creep, stress relaxation, and hysteresis. It has been shown that
preconditioning ACL grafts prior to reconstruction may reduce the
amount of stress relaxation by approximately 50%, compared with
ligament grafts with no preconditioning.

Many factors influence the biomechanical properties of
ligaments, including biochemistry, immobilization, and aging.
Stiffness, ultimate load, and energy absorbed at failure increase with
age and skeletal maturity, which may be attributable to further
tropocollagen chain cross-linking. As ligaments mature, the
bone-ligament-bone construct failure sites change. Rabbit MCL testing
has shown that younger rabbit ligaments fail by tibial avulsion and
mature ligaments fail by intrasubstance ligament tears. Ligament
immobilization causes intrasubstance and insertion site changes that
alter structural properties. Insertion sites reveal disruption of deep
fibers inserting into bone and osteoclastic activity that results in
subperiosteal bone resorption. Mobilization causes slow reversal of
these effects with ultimate load and energy absorbed at failure almost
reaching control levels.

Ligament injuries are graded according to tissue damage and instability (Table 1-1).
Extra-articular ligament healing passes through stages similar to
general wound healing. An inflammatory phase is followed by a
proliferative repair phase and, ultimately, a remodeling phase.

The mature healed ligament differs from normal tissue.
It has less tensile strength, usually 50% to 70% of normal. Mechanical
properties of healing intrasubstance MCL tears are inferior, but they
have a larger cross-sectional area than the intact MCL. Although the
healed ligament has lower tensile strength than an uninjured ligament,
it does not usually result in alteration of joint function. This may be
partially explained by the increased volume of the repaired tissue
compared with the uninjured ligament.