Bone Formation and Development

Discuss the process of bone formation and development.

 List the steps of intramembranous ossification

 Explain the role of cartilage in bone formation
 List the steps of endochondral ossification
 Explain the growth activity at the epiphyseal plate
 Explain how bones remodel overtime
 Compare and contrast the processes of intramembranous and endochondral bone formation
 Compare and contrast the interstitial and appositional growth

 In the early stages of embryonic development, the embryo’s skeleton consists of fibrous
membranes and hyaline cartilage.
 By the sixth or seventh week of embryonic life, the actual process of bone
development, ossification (osteogenesis), begins. There are two osteogenic pathways—
intramembranous ossification and endochondral ossification.

Osteogenic pathways

Intramembranous Endochondral
Ossification Ossification

Intramembranous Ossification

 During intramembranous ossification, compact and spongy bone develops directly

from sheets of mesenchymal (undifferentiated) connective tissue. The flat bones of the
face, most of the cranial bones, and the clavicles (collarbones) are formed.
 The process begins when mesenchymal cells in the embryonic skeleton gather together
and begin to differentiate into specialized cells (Figure 6.4.1a).
 Some of these cells will differentiate into capillaries, while others will become osteogenic
cells and then osteoblasts. Although they will ultimately be spread out by the formation
of bone tissue, early osteoblasts appear in a cluster called an ossification center.
  The osteoblasts secrete osteoid, uncalcified matrix consisting of collagen precursors and
other organic proteins, which calcifies (hardens) within a few days as mineral salts are
deposited on it, thereby entrapping the osteoblasts within. Once entrapped, the osteoblasts
become osteocytes (Figure 6.4.1b).
 Several clusters of osteoid unite around the capillaries to form a trabecular matrix, while
osteoblasts on the surface of the newly formed spongy bone become the cellular layer of
the periosteum (Figure 6.4.1c).
 The periosteum then secretes compact bone superficial to the spongy bone. The spongy
bone crowds nearby blood vessels, which eventually condense into red bone marrow
(Figure 6.4.1d).
 The new bone is constantly also remodeling under the action of osteoclasts (not shown).

(Figure 6.4.1)

Intramembranous ossification follows four steps.

(a) Mesenchymal cells group into clusters, differentiate into osteoblasts, and ossification
centers form.

(b) Secreted osteoid traps osteoblasts, which then become osteocytes.

(c) Trabecular matrix and periosteum form.

(d) Compact bone develops superficial to the trabecular bone, and crowded blood vessels
condense into red bone marrow.

Intramembranous ossification begins in utero during fetal development and continues on into
adolescence. At birth, the skull and clavicles are not fully ossified nor are the junctions between
the skull bone (sutures) closed. This allows the skull and shoulders to deform during passage
through the birth canal. The last bones to ossify via intramembranous ossification are the flat
bones of the face, which reach their adult size at the end of the adolescent growth spurt.

Endochondral Ossification

In endochondral ossification, bone develops by replacing hyaline cartilage. Cartilage does not
become bone. Instead, cartilage serves as a template to be completely replaced by new bone.
Endochondral ossification takes much longer than intramembranous ossification. Bones at the
base of the skull and long bones form via endochondral ossification.

In a long bone, for example, at about 6 to 8 weeks after conception, some of the mesenchymal
cells differentiate into chondroblasts (cartilage cells) that form the hyaline cartilaginous skeletal
precursor of the bones (Figure 6.4.2a).

This cartilage is a flexible, semi-solid matrix produced by chondroblasts and consists of

hyaluronic acid, chondroitin sulfate, collagen fibers, and water. As the matrix surrounds and
isolates chondroblasts, they are called chondrocytes.

Unlike most connective tissues, cartilage is avascular, meaning that it has no blood vessels
supplying nutrients and removing metabolic wastes. All of these functions are carried on by
diffusion through the matrix from vessels in the surrounding perichondrium.

covers the cartilage,a).

Figure 6.4.2 – Endochondral Ossification:
Endochondral ossification follows five steps. (a) Mesenchymal cells differentiate into
chondrocytes that produce a cartilage model of the future bony skeleton.
(b) Blood vessels on the edge of the cartilage model bring osteoblasts that deposit a bony
collar. (c) Capillaries penetrate cartilage and deposit bone inside cartilage model, forming
primary ossification center.
(d) Cartilage and chondrocytes continue to grow at ends of the bone while medullary cavity
expands and remodels.
(e) Secondary ossification centers develop after birth.
(f) Hyaline cartilage remains at epiphyseal (growth) plate and at joint surface as articular
cartilage.

As more and more matrix is produced, the cartilaginous model grow in size. Blood vessels in the
perichondrium bring osteoblasts to the edges of the structure and these arriving osteoblasts
deposit bone in a ring around the diaphysis – this is called a bone collar (Figure 6.4.2b).

The bony edges of the developing structure prevent nutrients from diffusing into the center of
the hyaline cartilage. This results in chondrocyte death and disintegration in the center of the
structure. These enlarging spaces eventually combine to become the medullary cavity. Bone is
now deposited within the structure creating the primary ossification center (Figure 6.4.2c).

While these deep changes are occurring, chondrocytes and cartilage continue to grow at the ends
of the structure (the future epiphyses), which increases the structure’s length at the same time
bone is replacing cartilage in the diaphyses.

This continued growth is accompanied by remodeling inside the medullary cavity (osteoclasts
were also brought with invading blood vessels) and overall lengthening of the structure (Figure
6.4.2d). By the time the fetal skeleton is fully formed, cartilage remains at the epiphyses and at
the joint surface as articular cartilage.

After birth, this same sequence of events (matrix mineralization, death of chondrocytes, invasion
of blood vessels from the periosteum, and seeding with osteogenic cells that become osteoblasts)
occurs in the epiphyseal regions, and each of these centers of activity is referred to as
a secondary ossification center (Figure 6.4.2e). Throughout childhood and adolescence, there
remains a thin plate of hyaline cartilage between the diaphysis and epiphysis known as
the growth or epiphyseal plate (Figure 6.4.2f). Eventually, this hyaline cartilage will be
removed and replaced by bone to become the epiphyseal line.
How Bones Grow in Length

The epiphyseal plate is the area of elongation in a long bone. It includes a layer of hyaline
cartilage where ossification can continue to occur in immature bones. We can divide the
epiphyseal plate into a diaphyseal side (closer to the diaphysis) and an epiphyseal side (closer to
the epiphysis). On the epiphyseal side of the epiphyseal plate, hyaline cartilage cells are active
and are dividing and producing hyaline cartilage matrix. (figure 6.43, reserve and proliferative
zones). On the diaphyseal side of the growth plate, cartilage calcifies and dies, then is replaced
by bone (figure 6.43, zones of hypertrophy and maturation, calcification and ossification). As
cartilage grows, the entire structure grows in length and then is turned into bone. Once cartilage
cannot grow further, the structure cannot elongate more.

The epiphyseal plate is composed of five zones of cells and activity (Figure 6.4.3). The reserve
zone is the region closest to the epiphyseal end of the plate and contains small chondrocytes
within the matrix. These chondrocytes do not participate in bone growth but secure the
epiphyseal plate to the overlying osseous tissue of the epiphysis.
Figure 6.4.3 – Longitudinal Bone Growth: The epiphyseal plate is responsible for longitudinal
bone growth.
The proliferative zone is the next layer toward the diaphysis and contains stacks of slightly
larger chondrocytes. It makes new chondrocytes (via mitosis) to replace those that die at the
diaphyseal end of the plate. Chondrocytes in the next layer, the zone of maturation and
hypertrophy, are older and larger than those in the proliferative zone. The more mature cells are
situated closer to the diaphyseal end of the plate. The longitudinal growth of bone is a result of
cellular division in the proliferative zone and the maturation of cells in the zone of maturation
and hypertrophy. This growth within a tissue is called interstitial growth.

Most of the chondrocytes in the zone of calcified matrix, the zone closest to the diaphysis, are
dead because the matrix around them has calcified, restricting nutrient diffusion. Capillaries and
osteoblasts from the diaphysis penetrate this zone, and the osteoblasts secrete bone tissue on the
remaining calcified cartilage. Thus, the zone of calcified matrix connects the epiphyseal plate to
the diaphysis. A bone grows in length when osseous tissue is added to the diaphysis.

Bones continue to grow in length until early adulthood. The rate of growth is controlled by
hormones, which will be discussed later. When the chondrocytes in the epiphyseal plate cease
their proliferation and bone replaces all the cartilage, longitudinal growth stops. All that remains
of the epiphyseal plate is the ossified epiphyseal line (Figure 6.4.4).

Figure 6.4.4 –
Progression from Epiphyseal Plate to Epiphyseal Line: As a bone matures, the epiphyseal
plate progresses to an epiphyseal line. (a) Epiphyseal plates are visible in a growing bone. (b)
Epiphyseal lines are the remnants of epiphyseal plates in a mature bone.
How Bones Grow in Diameter

While bones are increasing in length, they are also increasing in diameter; growth in diameter
can continue even after longitudinal growth ceases. This growth by adding to the free surface of
bone is called appositional growth. Appositional growth can occur at the endosteum or
peristeum where osteoclasts resorb old bone that lines the medullary cavity, while osteoblasts
produce new bone tissue. The erosion of old bone along the medullary cavity and the deposition
of new bone beneath the periosteum not only increase the diameter of the diaphysis but also
increase the diameter of the medullary cavity. This remodeling of bone primarily takes place
during a bone’s growth. However, in adult life, bone undergoes constant remodeling, in which
resorption of old or damaged bone takes place on the same surface where osteoblasts lay new
bone to replace that which is resorbed. Injury, exercise, and other activities lead to remodeling.
Those influences are discussed later in the chapter, but even without injury or exercise, about 5
to 10 percent of the skeleton is remodeled annually just by destroying old bone and renewing it
with fresh bone.

Diseases of the…Skeletal System

Osteogenesis imperfecta (OI) is a genetic disease in which bones do not form properly and
therefore are fragile and break easily. It is also called brittle bone disease. The disease is present
from birth and affects a person throughout life.

The genetic mutation that causes OI affects the body’s production of collagen, one of the critical
components of bone matrix. The severity of the disease can range from mild to severe. Those
with the most severe forms of the disease sustain many more fractures than those with a mild
form. Frequent and multiple fractures typically lead to bone deformities and short stature.
Bowing of the long bones and curvature of the spine are also common in people afflicted with
OI. Curvature of the spine makes breathing difficult because the lungs are compressed.

Because collagen is such an important structural protein in many parts of the body, people with
OI may also experience fragile skin, weak muscles, loose joints, easy bruising, frequent
nosebleeds, brittle teeth, blue sclera, and hearing loss. There is no known cure for OI. Treatment
focuses on helping the person retain as much independence as possible while minimizing
fractures and maximizing mobility. Toward that end, safe exercises, like swimming, in which the
body is less likely to experience collisions or compressive forces, are recommended. Braces to
support legs, ankles, knees, and wrists are used as needed. Canes, walkers, or wheelchairs can
also help compensate for weaknesses.

When bones do break, casts, splints, or wraps are used. In some cases, metal rods may be
surgically implanted into the long bones of the arms and legs. Research is currently being
conducted on using bisphosphonates to treat OI. Smoking and being overweight are especially
risky in people with OI, since smoking is known to weaken bones, and extra body weight puts
additional stress on the bones.
Muscle contraction 1

Muscle contraction
Muscle fiber generates tension through the
action of actin and myosin cross-bridge
cycling. While under tension, the muscle
may lengthen, shorten or remain the same.
Although the term 'contraction' implies
shortening, when referring to the muscular
system, it means muscle fibers generating
tension with the help of motor neurons (the
terms twitch tension, twitch force and fiber
contraction are also used).

Voluntary muscle contraction is controlled

by the central nervous system. Voluntary
muscle contraction occurs as a result of
conscious effort originating in the brain. The
brain sends signals, in the form of action A top-down view of skeletal muscle

potentials, through the nervous system to the

motor neuron that innervates several muscle fibers. In the case of some reflexes, the signal to contract can originate
in the spinal cord through a feedback loop with the grey matter. Involuntary muscles such as the heart or smooth
muscles in the gut and vascular system contract as a result of non-conscious brain activity or stimuli proceeding in
the body to the muscle itself.

Contractions, by muscle type

For voluntary muscles, contraction occurs as a result of conscious effort originating in the brain. The brain sends
signals, in the form of action potentials, through the nervous system to the motor neuron that innervates several
muscle fibers [1] . In the case of some reflexes, the signal to contract can originate in the spinal cord through a
feedback loop with the grey matter. Involuntary muscles such as the heart or smooth muscles in the gut and vascular
system contract as a result of non-conscious brain activity or stimuli endogenous to the muscle itself. Other actions
such as locomotion, breathing and chewing have a reflex aspect to them: the contractions can be initiated
consciously or unconsciously.
There are three general types of muscle tissues:
• Skeletal muscle responsible for movement
• Cardiac muscle responsible for pumping blood
• Smooth muscle responsible for sustained contractions in the blood vessels, gastrointestinal tract, and other areas
in the body
Skeletal and cardiac muscles are called striated muscle because of their striped appearance under a microscope,
which is due to the highly organized alternating pattern of A band and I band.
While nerve impulse profiles are, for the most part, always the same, skeletal muscles are able to produce varying
levels of contractile force. This phenomenon can be best explained by Force Summation. Force Summation describes
the addition of individual twitch contractions to increase the intensity of overall muscle contraction. This can be
achieved in two ways [2] : (1) by increasing the number and size of contractile units simultaneously, called multiple
fiber summation, and (2) by increasing the frequency at which action potentials are sent to muscle fibers, called
frequency summation.
Muscle contraction 2

• Multiple fiber summation – When a weak signal is sent by the CNS to contract a muscle, the smaller motor
units, being more excitable than the larger ones, are stimulated first. As the strength of the signal increases, more
motor units are excited in addition to larger ones, with the largest motor units having as much as 50 times the
contractile strength as the smaller ones. As more and larger motor units are activated, the force of muscle
contraction becomes progressively stronger. A concept known as the size principle allows for a gradation of
muscle force during weak contraction to occur in small steps, which then become progressively larger when
greater amounts of force are required.
• Frequency summation - For skeletal muscles, the force exerted by the muscle is controlled by varying the
frequency at which action potentials are sent to muscle fibers. Action potentials do not arrive at muscles
synchronously, and, during a contraction, some fraction of the fibers in the muscle will be firing at any given
time. In a typical circumstance, when a human is exerting a muscle as hard as he/she is consciously able, roughly
one-third of the fibers in that muscle will be firing at once, yet can be affected by various physiological and
psychological factors (including Golgi tendon organs and Renshaw cells). This 'low' level of contraction is a
protective mechanism to prevent avulsion of the tendon - the force generated by a 95% contraction of all fibers is
sufficient to damage the body.

Skeletal muscle contractions

Skeletal muscles contract according to
the sliding filament model:
1. An action potential originating in
the CNS reaches an alpha motor
neuron, which then transmits an
action potential down its own axon.
2. The action potential propagates by
activating voltage-gated sodium
channels along the axon toward the
synaptic cleft. Eventually, the
action potential reaches the motor
neuron terminal and causes a
calcium ion influx through the
voltage-gated calcium channels.
3. The Ca2+ influx causes vesicles
containing the neurotransmitter
acetylcholine to fuse with the plasma membrane, releasing acetylcholine out into the extracellular space between
the motor neuron terminal and the motor end plate of the skeletal muscle fiber.
4. The acetylcholine diffuses across the synapse and binds to and activates nicotinic acetylcholine receptors on the
motor end plate of
Muscle contraction 3

the muscle cell. Activation of the nicotinic receptor opens its

intrinsic sodium/potassium channel, causing sodium to rush in and
potassium to trickle out. Because the channel is more permeable to
sodium, the muscle fiber membrane becomes more positively
charged, triggering an action potential.
5. The action potential spreads through the muscle fiber's network of
T-tubules, depolarizing the inner portion of the muscle fiber.
6. The depolarization activates L-type voltage-dependent calcium
channels (dihydropyridine receptors) in the T tubule membrane,
which are in close proximity to calcium-release channels
(ryanodine receptors) in the adjacent sarcoplasmic reticulum.

7. Activated voltage-gated calcium channels physically interact with calcium-release channels to activate them,
causing the sarcoplasmic reticulum to release calcium.
8. The calcium binds to the troponin C present on the actin-containing thin filaments of the myofibrils. The troponin
then allosterically modulates the tropomyosin. Under normal circumstances, the tropomyosin sterically obstructs
binding sites for myosin on the thin filament; once calcium binds to the troponin C and causes an allosteric
change in the troponin protein, troponin T allows tropomyosin to move, unblocking the binding sites.
9. Myosin (which has ADP and inorganic phosphate bound to its nucleotide binding pocket and is in a ready state)
binds to the newly uncovered binding sites on the thin filament (binding to the thin filament is very tightly
coupled to the release of inorganic phosphate). Myosin is now bound to actin in the strong binding state. The
release of ADP and inorganic phosphate are tightly coupled to the power stroke (actin acts as a cofactor in the
release of inorganic phosphate, expediting the release). This will pull the Z-bands towards each other, thus
shortening the sarcomere and the I-band.
10. ATP binds myosin, allowing it to release actin and be in the weak binding state (a lack of ATP makes this step
impossible, resulting in the rigor state characteristic of rigor mortis). The myosin then hydrolyzes the ATP and
uses the energy to move into the "cocked back" conformation. In general, evidence (predicted and in vivo)
indicates that each skeletal muscle myosin head moves 10-12 nm each power stroke, however there is also
evidence (in vitro) of variations (smaller and larger) that appear specific to the myosin isoform.
11. Steps 9 and 10 repeat as long as ATP is available and calcium is present on thin filament.
12. While the above steps are occurring, calcium is actively pumped back into the sarcoplasmic reticulum. When
calcium is no longer present on the thin filament, the tropomyosin changes conformation back to its previous state
so as to block the binding sites again. The myosin ceases binding to the thin filament, and the contractions cease.
The calcium ions leave the troponin molecule in order to maintain the calcium ion concentration in the sarcoplasm.
The active pumping of calcium ions into the sarcoplasmic reticulum creates a deficiency in the fluid around the
Muscle contraction 4

myofibrils. This causes the removal of calcium ions from the troponin. Thus, the tropomyosin-troponin complex
again covers the binding sites on the actin filaments and contraction ceases.

Classification of voluntary muscular contractions

Skeletal muscle contractions can be broadly separated into twitch and tetanic contractions. In a twitch contraction, a
short burst of stimulation causes the muscle to contract, but the duration is so short that the muscle begins relaxing
before reaching peak force. The shape of the graph of force vs time in a twitch contraction can give information
about the relative rates of calcium release and re-uptake from the sarcoplasmic reticulum. If the stimulation is long
enough, the muscle reaches peak force and plateaus at this level, resulting in a tetanic contraction. If the stimulation
is not intense enough, force will oscilate during the plataeu and be submaximal, but with sufficient stimulation, there
will be a constant force level until stimulation stops.
Voluntary muscular contractions can be further classified according to either length changes or force levels. In spite
of the fact that the muscle actually shortens only in concentric contractions, all are typically referred to as
"contractions".
• In concentric contraction, the force generated is sufficient to overcome the resistance, and the muscle shortens as
it contracts. This is what most people think of as a muscle contraction.
• In eccentric contraction, the force generated is insufficient to overcome the external load on the muscle and the
muscle fibers lengthen as they contract. An eccentric contraction is used as a means of decelerating a body part or
object, or lowering a load gently rather than letting it drop.
• In isometric contraction, the muscle remains the same length. An example would be holding an object up without
moving it; the muscular force precisely matches the load, and no movement results.
• In isotonic contraction, the tension in the muscle remains constant despite a change in muscle length. This can
occur only when a muscle's maximal force of contraction exceeds the total load on the muscle.
• In isovelocity contraction (sometimes called "isokinetic"), the muscle contraction velocity remains constant, while
force is allowed to vary. True isovelocity contractions are rare in the body, and are primarily an analysis method
used in experiments on isolated muscles that have been dissected out of the organism.
In reality, muscles rarely perform under any sort of constant force, velocity, or speed, but these contractions are
useful for understanding overall muscle properties present in more complex contractions that occur in vivo. Cyclic in
vivo contractions can be modeled using work loops.

Smooth muscle contraction

The interaction of sliding actin and myosin filaments is similar in smooth muscle. There are differences in the
proteins involved in contraction in vertebrate smooth muscle compared to cardiac and skeletal muscle. Smooth
muscle does not contain troponin, but does contain the thin filament protein tropomyosin and other notable proteins -
caldesmon and calponin. Contractions are initiated by the calcium-activated phosphorylation of myosin rather than
calcium binding to troponin. Contractions in vertebrate smooth muscle are initiated by agents that increase
intracellular calcium. This is a process of depolarizing the sarcolemma and extracellular calcium entering through
L-type calcium channels, and intracellular calcium release predominately from the sarcoplasmic reticulum. Calcium
release from the sarcoplasmic reticulum is from Ryanodine receptor channels (calcium sparks) by a redox process
and Inositol triphosphate receptor channels by the second messenger inositol triphosphate. The intracellular calcium
binds with calmodulin, which then binds and activates myosin light-chain kinase. The calcium-calmodulin-myosin
light-chain kinase complex phosphorylates myosin on the 20 kilodalton (kDa) myosin light chains on amino acid
residue-serine 19, initiating contraction and activating the myosin ATPase. The phosphorylation of caldesmon and
calponin by various kinases is suspected to play a role in smooth muscle contraction.
Phosphorylation of the 20 kDa myosin light chains correlates well with the shortening velocity of smooth muscle.
During this period, there is a rapid burst of energy utilization as measured by oxygen consumption. Within a few
Muscle contraction 5

minutes of initiation, the calcium level markedly decreases, the 20 kDa myosin light chains' phosphorylation
decreases, and energy utilization decreases; however, force in tonic smooth muscle is maintained. During contraction
of muscle, rapidly cycling crossbridges form between activated actin and phosphorylated myosin, generating force. It
is hypothesized that the maintenance of force results from dephosphorylated "latch-bridges" that slowly cycle and
maintain force. A number of kinases such as Rho kinase, Zip kinase, and Protein Kinase C are believed to participate
in the sustained phase of contraction, and calcium flux may be significant.

Invertebrate smooth muscles

In invertebrate smooth muscle, contraction is initiated with calcium directly binding to myosin and then rapidly
cycling cross-bridges generating force. Similar to vertebrate tonic smooth muscle, there is a low calcium and low
energy utilization catch phase. This sustained phase or catch phase has been attributed to a catch protein that is
similar to myosin light-chain kinase and titin, called twitchin.

Contractions

Concentric contraction
A concentric contraction is a type of muscle contraction in which the muscles shorten while generating force.
During a concentric contraction, a muscle is stimulated to contract according to the sliding filament mechanism. This
occurs throughout the length of the muscle, generating force at the musculo-tendinous junction, causing the muscle
to shorten and changing the angle of the joint. In relation to the elbow, a concentric contraction of the biceps would
cause the arm to bend at the elbow and hand to move from near to the leg, to close to the shoulder (a biceps curl). A
concentric contraction of the triceps would change the angle of the joint in the opposite direction, straightening the
arm and moving the hand towards the leg.

Eccentric contraction
During an eccentric contraction, the muscle elongates while under tension due to an opposing force being greater
than the force generated by the muscle.[3] Rather than working to pull a joint in the direction of the muscle
contraction, the muscle acts to decelerate the joint at the end of a movement or otherwise control the repositioning of
a load. This can occur involuntarily (when attempting to move a weight too heavy for the muscle to lift) or
voluntarily (when the muscle is 'smoothing out' a movement). Over the short-term, strength training involving both
eccentric and concentric contractions appear to increase muscular strength more than training with concentric
contractions alone.[4]
During an eccentric contraction of the biceps muscle, the elbow starts the movement while bent and then straightens
as the hand moves away from the shoulder. During an eccentric contraction of the triceps muscle, the elbow starts
the movement straight and then bends as the hand moves towards the shoulder. Desmin, titin, and other z-line
proteins are involved in eccentric contractions, but their mechanism is poorly understood in comparison to
cross-bridge cycling in concentric contractions.[3]
Muscles undergoing heavy eccentric loading suffer greater damage when overloaded (such as during muscle
building or strength training exercise) as compared to concentric loading. When eccentric contractions are used in
weight training, they are normally called negatives. During a concentric contraction, muscle fibers slide across each
other, pulling the Z-lines together. During an eccentric contraction, the filaments slide past each other the opposite
way, though the actual movement of the myosin heads during an eccentric contraction is not known. Exercise
featuring a heavy eccentric load can actually support a greater weight (muscles are approximately 10% stronger
during eccentric contractions than during concentric contractions) and also results in greater muscular damage and
delayed onset muscle soreness one to two days after training. Exercise that incorporates both eccentric and
concentric muscular contractions (i.e. involving a strong contraction and a controlled lowering of the weight) can
Muscle contraction 6

produce greater gains in strength than concentric contractions alone.[4] [5] While unaccustomed heavy eccentric
contractions can easily lead to overtraining, moderate training may confer protection against injury.[4]

Eccentric contractions in movement

Eccentric contractions normally occur as a braking force in opposition to a concentric contraction to protect joints
from damage. During virtually any routine movement, eccentric contractions assist in keeping motions smooth, but
can also slow rapid movements such as a punch or throw. Part of training for rapid movements such as pitching
during baseball involves reducing eccentric braking allowing a greater power to be developed throughout the
movement.
Eccentric contractions are being researched for their ability to speed rehab of weak or injured tendons. Achilles
tendinitis has been shown to benefit from high-load eccentric contractions.[6] [7]

Isometric contraction
An isometric contraction of a muscle generates force without changing length. An example can be found when the
muscles of the hand and forearm grip an object; the joints of the hand do not move, but muscles generate sufficient
force to prevent the object from being dropped.

Force-length and Force-velocity relationships

Unlike mechanical systems such as motors, the force a muscle can generate depends upon both the length and
shortening velocity of the muscle.
Force-Length relationship, also called the Length-Tension curve,
relates the strength of an isometric contraction to the length of the
muscle at which the contraction occurs. Muscles operate with
greatest active force when close to an ideal length (often their
resting length). When stretched or shortened beyond this (whether
due to the action of the muscle itself or by an outside force), the
maximum active force generated decreases[8] . This decrease is
Muscle length vs. Force.
minimal for small deviations, but the force drops off rapidly as the
length deviates further from the ideal. As a result, in most
biological systems, the range of muscle contraction will remain on the peak of the length-tension curve, in order to
maximize contraction force. Due to the presence of elastic proteins within a muscle, as the muscle is stretched
beyond a given length, there is an entirely passive force, which opposes lengthening. Combined together, we see a
strong resistance to lengthening an active muscle far beyond the peak of active force.

Force-Velocity relationship: The speed at which a muscle changes

length (usually regulated by external forces, such as load or other
muscles) also affects the force it can generate. Force declines in a
hyperbolic fashion relative to the isometric force as the shortening
velocity increases, eventually reaching zero at some maximum
velocity. The reverse holds true for when the muscle is stretched -
force increases above isometric maximum, until finally reaching
Muscle shortening velocity vs. Force & Power.
an absolute maximum. This has strong implications for the rate at
which muscles can perform mechanical work (power). Since
power is equal to force times velocity, the muscle generates no power at either isometric force (due to zero velocity)
or maximal velocity (due to zero force). Instead, the optimal shortening velocity for power generation is
approximately one-third of maximum shortening velocity.
Muscle contraction 7

These two fundamental properties of muscle have numerous biomechanical consequences, including limiting
running speed, strength, and jumping distance and height.

See also
• Exercise physiology
• Cramp
• Dystonia
• Fasciculation
• Hypnic jerk
• In_vitro_muscle_testing
• Myoclonus
• Spasm
• Supination

Additional images

Phase 1 Phase 2 Phase 3 Phase 4

References
[1] Tassinary & Cacioppo (2000), "The Skeletomotor system: surface electromyography", Handbook of psychophysiology, Second edition, Ed.
John T. Cacioppo, Luois G. Tassinary, Gary G. Berntson
[2] E. Shwedyk, R. Balasubramanian, R. N. Scott (1977), "A nonstationary model for the Electromyogram", IEEE Transactions on Biomedical
Engineering, Vol. 24, No. 5, September
[3] "Types of contractions" (http:/ / muscle. ucsd. edu/ musintro/ contractions. shtml). 2006-05-31. . Retrieved 2007-10-02.
[4] Colliander EB, Tesch PA (1990). "Effects of eccentric and concentric muscle actions in resistance training". Acta Physiol. Scand. 140 (1):
31–9. doi:10.1111/j.1748-1716.1990.tb08973.x. PMID 2275403.
[5] Brooks, G.A; Fahey, T.D. & White, T.P. (1996). Exercise Physiology: Human Bioenergetics and Its Applications. (2nd ed.).. Mayfield
Publishing Co.
[6] Alfredson H, Pietilä T, Jonsson P, Lorentzon R (1998). "Heavy-load eccentric calf muscle training for the treatment of chronic Achilles
tendinosis" (http:/ / ajs. sagepub. com/ cgi/ pmidlookup?view=long& pmid=9617396). Am J Sports Med 26 (3): 360–6. PMID 9617396. .
[7] Satyendra1,, L; Byl N (2006). Effectiveness of physical therapy for Achilles tendinopathy: An evidence based review of eccentric exercises
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External links
• Animation: Myofilament Contraction (http://highered.mcgraw-hill.com/sites/0072495855/student_view0/
chapter10/animation__myofilament_contraction.html)
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 Physiological role of hemoglobin in oxygen and CO2 transport.

Hemoglobin is a critical protein in the human body responsible for transporting oxygen
(O2) and carbon dioxide (CO2) between the lungs and the body's tissues. It plays a pivotal role
in maintaining the body's overall homeostasis and ensuring that oxygen reaches cells and tissues
while facilitating the removal of carbon dioxide, a waste product of cellular metabolism. Let's
delve into the physiological roles of hemoglobin in oxygen and CO2 transport:
1. Oxygen Transport: Hemoglobin's primary role is to bind with oxygen in the lungs, where
oxygen levels are high due to the respiratory process. Hemoglobin is composed of four protein
subunits, each of which contains an iron atom (heme group) that can bind to an oxygen molecule.
When hemoglobin encounters oxygen in the lungs, it forms oxyhemoglobin, which has a higher
affinity for oxygen. This facilitates the loading of oxygen onto hemoglobin in the lungs, where
the partial pressure of oxygen is high, and the formation of oxyhemoglobin is favored.

As blood circulates through the body's arteries, oxyhemoglobin releases its oxygen to cells and
tissues with lower oxygen partial pressures. This occurs due to a phenomenon called the Bohr
effect, where factors such as pH and CO2 concentration affect hemoglobin's oxygen-binding
affinity. In tissues with higher levels of CO2 (which forms carbonic acid when dissolved in
water, lowering pH), hemoglobin's affinity for oxygen decreases. This encourages the release of
oxygen from hemoglobin, allowing it to diffuse into the cells where oxygen is needed for cellular
respiration.
2. Carbon Dioxide Transport: Hemoglobin also plays a role in carrying carbon dioxide, primarily
in the form of bicarbonate ions (HCO3-) as part of the bicarbonate buffer system. As cells
metabolize nutrients, they produce carbon dioxide as a waste product. Carbon dioxide diffuses
into red blood cells, where it reacts with water to form carbonic acid (H2CO3) with the help of
an enzyme called carbonic anhydrase.
Carbonic acid is unstable and dissociates into bicarbonate ions and hydrogen ions. Bicarbonate
ions are then transported out of the red blood cells into the plasma in exchange for chloride ions
through a process known as the chloride shift. This exchange helps maintain charge neutrality
within the cell. The hydrogen ions generated in this process bind to hemoglobin, reducing its
affinity for oxygen and encouraging the release of oxygen in tissues where it is needed.
The transport of bicarbonate ions to the lungs occurs via the reverse process. In the lungs, where
oxygen levels are high, the binding of oxygen to hemoglobin displaces hydrogen ions from
hemoglobin. This results in the release of hydrogen ions, which can combine with bicarbonate
ions to reform carbonic acid. Carbonic anhydrase then catalyzes the conversion of carbonic acid
back into carbon dioxide and water. The released carbon dioxide is exhaled from the lungs
during respiration.

In summary, hemoglobin's ability to reversibly bind to oxygen and carbon dioxide, as well as its
sensitivity to factors like pH and CO2 concentration, allows it to facilitate efficient oxygen
uptake in the lungs and oxygen release in the tissues, while also aiding in the transport of carbon
dioxide from the tissues to the lungs for elimination. This dynamic interplay ensures the
maintenance of proper oxygen and carbon dioxide levels in the body, supporting cellular
metabolism and overall physiological function.
 Mechanism Of Breathing

The processes of inspiration (breathing in) and expiration (breathing out) are vital for
providing oxygen to tissues and removing carbon dioxide from the body. Inspiration occurs
via active contraction of muscles – such as the diaphragm – whereas expiration tends to be
passive, unless it is forced.

In this article, we shall look at the physiology of ventilation – the process of inspiration and
expiration, how this differs between quiet and forced breathing, and their clinical
correlations.

The space between the outer surface of the lungs and inner thoracic wall is known as
the pleural space. This is usually filled with pleural fluid, forming a seal which holds the
lungs against the thoracic wall by the force of surface tension. This seal ensures that when
the thoracic cavity expands or reduces, the lungs undergo expansion or reduction in size
accordingly.

During breathing, the contraction and relaxation of muscles acts to change the volume of the
thoracic cavity. As the thoracic cavity and lungs move together, this changes the volume of
the lungs, in turn changing the pressure inside the lungs.

Boyle’s law states that the volume of gas is inversely proportional to pressure (when
temperature is constant). Therefore:

 When the volume of the thoracic cavity increases – the volume of the lungs increases and
the pressure within the lungs decreases.
 When the volume of the thoracic cavity decreases – the volume of the lungs decreases and
the pressure within the lungs increases.
 Process of Inspiration
Inspiration is the phase of ventilation in which air enters the lungs. It is initiated by contraction
of the inspiratory muscles:

 Diaphragm – flattens, extending the superior/inferior dimension of the thoracic cavity.

 External intercostal muscles – elevate the ribs and sternum, extending the anterior/posterior
dimension of the thoracic cavity.

The action of the inspiratory muscles results in an increase in the volume of the thoracic cavity.
As the lungs are held against the inner thoracic wall by the pleural seal, they also undergo an
increase in volume.

As per Boyle’s law, an increase in lung volume results in a decrease in the pressure within the
lungs. The pressure of the environment external to the lungs is now greater than the
environment within the lungs, meaning air moves into the lungs down the pressure gradient.
 Process of Passive Expiration
Expiration is the phase of ventilation in which air is expelled from the lungs. It is initiated by
the relaxation of the inspiratory muscles:

 Diaphragm – relaxes to return to its resting position, reducing the superior/inferior

dimension of the thoracic cavity.
 External intercostal muscles – relax to depress the ribs and sternum, reducing the
anterior/posterior dimension of the thoracic cavity.

The relaxation of the inspiratory muscles results in a decrease in the volume of the thoracic
cavity. The elastic recoil of the previously expanded lung tissue allows them to return to their
original size.

As per Boyle’s law, a decrease in lung volume results in an increase in the pressure within
the lungs. The pressure inside the lungs is now greater than in the external environment,
meaning air moves out of the lungs down the pressure gradient.
Forced Breathing
Forced breathing is an active mode of breathing which utilises additional muscles to rapidly
expand and contract the thoracic cavity volume. It most commonly occurs during exercise.
 Active Inspiration
Active inspiration involves the contraction of the accessory muscles of breathing (in
addition to those of quiet inspiration, the diaphragm and external intercostals). All of these
muscles act to increase the volume of the thoracic cavity:

 Scalenes – elevates the upper ribs.

 Sternocleidomastoid – elevates the sternum.
 Pectoralis major and minor – pulls ribs outwards.
 Serratus anterior – elevates the ribs (when the scapulae are fixed).
 Latissimus dorsi – elevates the lower ribs.

Active Expiration
Active expiration utilises the contraction of several thoracic and abdominal muscles. These
muscles act to decrease the volume of the thoracic cavity:

 Anterolateral abdominal wall – increases the intra-abdominal pressure, pushing the

diaphragm further upwards into the thoracic cavity.
 Internal intercostal – depresses the ribs.
 Innermost intercostal – depresses the ribs