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109 12.1 Case Study: Muscles and Movement

Created by CK-12 Foundation/Adapted by Christine Miller

Case Study: Needing to Relax

This dog (Figure 12.1.1) is expressing his interest in something — perhaps a piece of food — by using the neck muscles to tilt its head in an adorable fashion. Humans also sometimes tilt their heads to express interest. But imagine how disturbing and painful it would be if your neck tilted involuntarily, without you being able to control it! Forty-three year old Edward unfortunately knows just how debilitating this can be.

Edward has a rare condition called cervical dystonia , which is also called spasmodic torticollis. In this condition, the muscles in the neck contract involuntarily, often causing the person’s head to twist to one side. Figure 12.1.2 shows one type of abnormal head positioning that can be caused by cervical dystonia. The muscles may contract in a sustained fashion, holding the head and neck in one position, or they may spasm repeatedly, causing jerky movements of the head and neck.

Cervical dystonia is painful and can significantly interfere with a person’s ability to carry out their usual daily activities. In Edward’s case, he can no longer drive a car, because his uncontrollable head and neck movements and abnormal head positioning prevent him from navigating the road safely. He also has severe neck and shoulder pain much of the time.

Although it can be caused by an injury, there is no known cause of cervical dystonia — and there is also no cure. Fortunately for Edward, and others who suffer from cervical dystonia,  there is a treatment that can significantly reduce symptoms in many people. You may be surprised to learn that this treatment is the same substance which, when injected into the face, is used for cosmetic purposes to reduce wrinkles!

The substance is botulinum toxin, one preparation of which may be familiar to you by its brand name — Botox . It is a neurotoxin produced by the bacterium  Clostridium botulinum , and can cause a life-threatening illness called botulism . However, when injected in very small amounts by a skilled medical professional, botulinum toxins have some safe and effective uses. In addition to cervical dystonia, botulinum toxins can be used to treat other disorders involving the muscular system, such as strabismus (misalignment of the eyes); eye twitches; excessive muscle contraction due to neurological conditions like cerebral palsy; and even overactive bladder.

Botulinum toxin has its effect on the muscular system by inhibiting muscle contractions. When used to treat wrinkles, it relaxes the muscles of the face, lessening the appearance of wrinkles. When used to treat cervical dystonia and other disorders involving excessive muscle contraction, it reduces the abnormal contractions.

In this chapter, you will learn about the muscles of the body, how they contract to produce movements and carry out their functions, and some disorders that affect the muscular system. At the end of the chapter, you will find out if botulinum toxin helped relieve Edward’s cervical dystonia, and how this toxin works to inhibit muscle contraction.

Chapter Overview: Muscular System

In this chapter, you will learn about the muscular system, which carries out both voluntary body movements and involuntary contractions of internal organs and structures. Specifically, you will learn about:

• The different types of muscle tissue — skeletal, cardiac, and smooth muscle — and their different characteristics and functions.
• How muscle cells are specialized to contract and cause voluntary and involuntary movements.
• The ways in which muscle contraction is controlled.
• How skeletal muscles can grow or shrink, causing changes in strength.
• The structure and organization of skeletal muscles, including the different types of muscle fibres, and how actin and myosin filaments move across each other — according to the sliding filament theory — to cause muscle contraction.
• Cardiac muscle tissue in the heart that contracts to pump blood through the body.
• Smooth muscle tissue that makes up internal organs and structures, such as the digestive system, blood vessels, and uterus.
• The physical and mental health benefits of aerobic and anaerobic exercise, such as running and weight lifting.
• How individuals vary in their response to exercise.
• Disorders of the muscular system, including musculoskeletal disorders (such as strains and carpal tunnel syndrome) and neuromuscular disorders (such as muscular dystrophy, myasthenia gravis, and Parkinson’s disease).

As you read the chapter, think about the following questions:

• How is the contraction of skeletal muscles controlled?
• Botulinum toxin works on the cellular and molecular level to inhibit muscle contraction. Based on what you learn about how muscle contraction works, can you think of some ways it could potentially be inhibited?
• What is one disorder involving a lack of sufficient muscle contraction? Why does it occur?

Attributions

Figure 12.1.1

Whiskey’s 2nd Birthday by Kelly Hunter on Flickr is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/) license.

Figure 12.1.2

1024px-Dystonia2010 by James Heilman, MD on Wikimedia Commons is used under a  CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) license.

Botulism [online article]. (2018, January 10). World Health Organization (WHO). https://www.who.int/news-room/fact-sheets/detail/botulism

Mayo Clinic Staff. (n.d.) Cervical dystonia [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/cervical-dystonia/symptoms-causes/syc-20354123

A drug prepared from the bacterial toxin botulin, used medically to treat certain muscular conditions and cosmetically to remove wrinkles by temporarily paralyzing facial muscles.

A soft tissue that composes muscles in animal bodies, and gives rise to muscles' ability to contract. This is opposed to other components or tissues in muscle such as tendons or perimysium.

Actions which take place according to the one's desire or are under control.

Actions which are not under one's conscious control.

Voluntary, striated muscle that is attached to bones of the skeleton and helps the body move.

Involuntary, striated muscle found only in the walls of the heart; also called myocardium.

An involuntary, nonstriated muscle that is found in the walls of internal organs such as the stomach.

Human Biology Copyright © 2020 by Christine Miller is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License , except where otherwise noted.

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12.2 Introduction to the Muscular System

Created by CK-12 Foundation/Adapted by Christine Miller

Marvelous Muscles

Does the word  muscle make you think of the well-developed muscles of a weightlifter, like the woman in Figure 12.2.1? Her name is Natalia Zabolotnaya , and she’s a Russian Olympian. The muscles that are used to lift weights are easy to feel and see, but they aren’t the only muscles in the human body. Many muscles are deep within the body, where they form the walls of internal organs and other structures. You can flex your biceps at will, but you can’t control internal muscles like these. It’s a good thing that these internal muscles work without any conscious effort on your part, because movement of these muscles is essential for survival. Muscles are the organs of the muscular system.

What Is the Muscular System?

The  muscular system consists of all the muscles of the body. The largest percentage of muscles in the muscular system consists of skeletal muscles , which are attached to bones and enable voluntary body movements (shown in Figure 12.2.2). There are almost 650 skeletal muscles in the human body, many of them shown in Figure 12.2.2. Besides skeletal muscles, the muscular system also includes cardiac muscle , which makes up the walls of the heart, and smooth muscles , which control movement in other internal organs and structures.

Muscle Structure and Function

Muscles are organs composed mainly of muscle cells, which are also called  muscle fibres (mainly in skeletal and cardiac muscle) or  myocytes  (mainly in smooth muscle). Muscle cells are long, thin cells that are specialized for the function of contracting. They contain protein filaments that slide over one another using energy in ATP . The sliding filaments increase the tension in — or shorten the length of — muscle cells, causing a contraction. Muscle contractions are responsible for virtually  all  the movements of the body, both inside and out.

Skeletal muscles are attached to bones of the skeleton. When these muscles contract, they move the body. They allow us to use our limbs in a variety of ways, from walking to turning cartwheels. Skeletal muscles also maintain posture and help us to keep balance.

Smooth muscles in the walls of blood vessels contract to cause vasoconstriction , which may help conserve body heat. Relaxation of these muscles causes vasodilation , which may help the body lose heat. In the organs of the digestive system, smooth muscles squeeze food through the gastrointestinal tract by contracting in sequence to form a wave of muscle contractions called  peristalsis .  Think of squirting toothpaste through a tube by applying pressure in sequence from the bottom of the tube to the top, and you have a good idea of how food is moved by muscles through the digestive system. Peristalsis of smooth muscles also moves urine through the urinary tract.

Cardiac muscle tissue is found only in the walls of the heart. When cardiac muscle contracts, it makes the heart beat. The pumping action of the beating heart keeps blood flowing through the cardiovascular system.

Muscle Hypertrophy and Atrophy

Muscles can grow larger, or  hypertrophy .  This generally occurs through increased use, although hormonal or other influences can also play a role. The increase in testosterone that occurs in males during puberty, for example, causes a significant increase in muscle size. Physical exercise that involves weight bearing or resistance training can increase the size of skeletal muscles in virtually everyone. Exercises (such as running) that increase the heart rate may also increase the size and strength of cardiac muscle. The size of muscle, in turn, is the main determinant of muscle strength, which may be measured by the amount of force a muscle can exert.

Muscles can also grow smaller, or  atrophy , which can occur through lack of physical activity or from starvation. People who are immobilized for any length of time — for example, because of a broken bone or surgery — lose muscle mass relatively quickly. People in concentration or famine camps may be so malnourished that they lose much of their muscle mass, becoming almost literally just “skin and bones.” Astronauts on the International Space Station may also lose significant muscle mass because of weightlessness in space (see Figure 12.2.3).

Many diseases, including cancer and AIDS , are often associated with muscle atrophy. Atrophy of muscles also happens with age. As people grow older, there is a gradual decrease in the ability to maintain skeletal muscle mass, known as  sarcopenia .  The exact cause of sarcopenia is not known, but one possible cause is a decrease in sensitivity to growth factors that are needed to maintain muscle mass. Because muscle size determines strength, muscle atrophy causes a corresponding decline in muscle strength.

In both hypertrophy and atrophy, the number of muscle fibres does not change. What changes is the size of the muscle fibres. When muscles hypertrophy, the individual fibres become wider. When muscles atrophy, the fibres become narrower.

Interactions with Other Body Systems

Muscles cannot contract on their own. Skeletal muscles need stimulation from motor neurons in order to contract. The point where a motor neuron attaches to a muscle is called a  neuromuscular junction . Let’s say you decide to raise your hand in class. Your brain sends electrical messages through motor neurons to your arm and shoulder. The motor neurons, in turn, stimulate muscle fibres in your arm and shoulder to contract, causing your arm to rise.

Involuntary contractions of smooth and cardiac muscles are also controlled by electrical impulses, but in the case of these muscles, the impulses come from the autonomic nervous system (smooth muscle) or specialized cells in the heart (cardiac muscle). Hormones and some other factors also influence involuntary contractions of cardiac and smooth muscles. For example, the fight-or-flight hormone adrenaline increases the rate at which cardiac muscle contracts, thereby speeding up the heartbeat.

Muscles cannot move the body on their own. They need the skeletal system to act upon. The two systems together are often referred to as the  musculoskeletal system . Skeletal muscles are attached to the skeleton by tough connective tissues called  tendons . Many skeletal muscles are attached to the ends of bones that meet at a joint . The muscles span the joint and connect the bones. When the muscles contract, they pull on the bones, causing them to move. The skeletal system provides a system of levers that allow body movement. The muscular system provides the force that moves the levers.

12.2 Summary

• The muscular system consists of all the muscles of the body. There are three types of muscle: skeletal muscle (which is attached to bones and enables voluntary body movements), cardiac muscle (which makes up the walls of the heart and makes it beat), and smooth muscle (which is found in the walls of internal organs and other internal structures and controls their movements).
• Muscles are organs composed mainly of muscle cells, which may also be called muscle fibres or myocytes . Muscle cells are specialized for the function of contracting, which occurs when protein filaments inside the cells slide over one another using energy in ATP .
• Muscles can grow larger, or hypertrophy . This generally occurs through increased use (physical exercise), although hormonal or other influences can also play a role. Muscles can also grow smaller, or atrophy . This may occur through lack of use, starvation, certain diseases, or aging. In both hypertrophy and atrophy, the size — but not the number — of muscle fibres changes. The size of muscles is the main determinant of muscle strength.
• Skeletal muscles need the stimulus of motor neurons to contract, and to move the body, they need the skeletal system to act upon. Involuntary contractions of cardiac and smooth muscles are controlled by special cells in the heart, nerves of the autonomic nervous system , hormones, or other factors.

12.2 Review Questions

• What is the muscular system?
• Describe muscle cells and their function.
• Identify three types of muscle tissue and where each type is found.
• Define muscle hypertrophy and muscle atrophy.
• What are some possible causes of muscle hypertrophy?
• Give three reasons that muscle atrophy may occur.
• How do muscles change when they increase or decrease in size?
• How do changes in muscle size affect strength?
• Explain why astronauts can easily lose muscle mass in space.
• Describe how the terms  muscle cells ,  muscle fibres , and  myocytes  relate to each other.
• Name two systems in the body that work together with the muscular system to carry out movements.
• Describe one way in which the muscular system is involved in regulating body temperature.

12.2 Explore More

How your muscular system works – Emma Bryce, TED-Ed, 2017.

3D Medical Animation – Peristalsis in Large Intestine/Bowel || ABP ©, AnimatedBiomedical, 2013.

Muscle matters: Dr Brendan Egan at TEDxUCD, TEDx Talks, 2014.

Attributions

Figure 12.2.1

Natalia_Zabolotnaya_2012b by Simon Q on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/deed.en) license.

Figure 12.2.2

Bougle_whole2_retouched by Bouglé, Julien from the National LIbrary of Medicine (NLM) on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 12.2.3

Daniel_Tani_iss016e027910 by NASA/ International Space Station Imagery on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

AnimatedBiomedical. (2013, January 30). 3D Medical animation – Peristalsis in large intestine/bowel || ABP ©. YouTube. https://www.youtube.com/watch?v=Ujr0UAbyPS4&feature=youtu.be

Bouglé, J. (1899). Le corps humain en grandeur naturelle : planches coloriées et superposées, avec texte explicatif. J. B. Baillière et fils. In Historical Anatomies on the Web . http://www.nlm.nih.gov/exhibition/historicalanatomies/bougle_home.html

TED-Ed. (2017, October 26). How your muscular system works – Emma Bryce. YouTube. https://www.youtube.com/watch?v=VVL-8zr2hk4&feature=youtu.be

TEDx Talks. (2014, June 27). Muscle matters: Dr Brendan Egan at TEDxUCD. YouTube. https://www.youtube.com/watch?v=LkXwfTsqQgQ&feature=youtu.be

Wikipedia contributors. (2020, June 15). Natalya Zabolotnaya. In  Wikipedia.  https://en.wikipedia.org/w/index.php?title=Natalya_Zabolotnaya&oldid=962630409

The body system responsible for the movement of the human body. Attached to the bones of the skeletal system are about 700 named muscles that make up roughly half of a person's body weight. Each of these muscles is a discrete organ constructed of skeletal muscle tissue, blood vessels, tendons, and nerves.

Voluntary, striated muscle that is attached to bones of the skeleton and helps the body move.

Involuntary, striated muscle found only in the walls of the heart; also called myocardium.

An involuntary, nonstriated muscle that is found in the walls of internal organs such as the stomach.

A long, thin muscle cell that has the ability to contract.

A type of muscle cell that makes up smooth muscle tissue.

A complex organic chemical that provides energy to drive many processes in living cells, e.g. muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer.

A narrowing of blood vessels so less blood can flow through them.

The widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, which is the narrowing of blood vessels.

A distinctive pattern of smooth muscle contractions that propels foodstuffs distally through the esophagus and intestines.

An increase in the size of a structure, such as an increase in the size of a muscle through exercise.

The male sex hormone secreted mainly by the testes.

The decrease in the size of a structure, such as a decrease in the size of a muscle through non-use.

A group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.

Acquired Immunodeficiency Syndrome - a chronic, potentially life-threatening condition caused by the human immunodeficiency virus (HIV). By damaging your immune system, HIV interferes with your body's ability to fight infection and disease.

A gradual decrease in the ability to maintain skeletal muscle mass that occurs in later adulthood.

A chemical synapse where a motor neuron transmits a signal to a muscle fiber to initiate a muscle contraction.

division of the peripheral nervous system that controls involuntary activities

A hormone is a signaling molecule produced by glands in multicellular organisms that target distant organs to regulate physiology and behavior.

A body system which provides form, support, stability, and movement to the body. It is made up of the bones of the skeleton, muscles, cartilage, tendons, ligaments, joints, and other connective tissue that supports and binds tissues and organs together.

Dense fibrous connective tissue that attaches skeletal muscle to bones.

A structure where two or more bones of the skeleton come together.

Actions which take place according to the one's desire or are under control.

Actions which are not under one's conscious control.

Human Biology Copyright © 2020 by Christine Miller is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License , except where otherwise noted.

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Sarepta Gene Therapy Misses in Phase 3; Prospects Now Rely on FDA Flexibility

Sarepta Therapeutics’ Duchenne muscular dystrophy gene therapy fell short of its main Phase 3 goal, but the firm contends the full body of evidence supports expanding the therapy’s label to all patients who have the muscle-wasting disease. Analysts say prospects of the therapy, Elevidys, rest on FDA willingness to exercise flexibility it has already shown to rare disease drugmakers, including Sarepta.

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A Duchenne muscular dystrophy gene therapy available under accelerated FDA approval has failed to meet the main goal of a study designed to confirm patient benefit and support expansion of the one-time treatment to a broader age range of patients. But the therapy’s maker, Sarepta Therapeutics, points to success across the study’s secondary goals and it aims to seek a broader FDA approval based on “the totality of evidence.”

Accelerated approval of the gene therapy, Elevidys, covers children ages 4 and 5 who have Duchenne , an inherited muscle-weakening disorder that leads to difficulty sitting up, walking, and eventually breathing. The confirmatory Phase 3 study enrolled children ages 4 to 7. The main goal of the placebo-controlled study was to show, at 52 weeks, a change in score according to a 17-point assessment that measures motor function in Duchenne patients.

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According to preliminary results Sarepta released late Monday, patients in the Elevidys group showed an improvement of 2.6 points—not enough to be statistically significant compared to the 1.9 point score change in the placebo arm. Despite that miss, Sarepta noted that the therapy led to statistically significant improvement on all pre-specified secondary endpoints, which included other measures of muscle function such as the time to rise, a 10-meter walk test, and measures of mobility and upper limb function. Speaking on a conference call, Sarepta President and CEO Doug Ingram said the preliminary data from the Phase 3 study have been shared with the FDA.

“On that basis, we are pursuing an application to expand the label of Elevidys and they have confirmed they are open to evaluating an application to expand the label,” he said. “Our goal is to expand the label to cover all amenable Duchenne patients without regard to age or ambulatory status.”

Investors signaled their disappointment with the results. Shares of Cambridge, Massachusetts-based Sarepta opened Tuesday at $57.63 apiece, down more than 46% from Monday’s closing price.

Duchenne, which primarily affects boys, stems from an inherited lack of dystrophin, a protein key to muscle function. Elevidys is an engineered version of the gene that codes for dystrophin. This gene does not code for full-length dystrophin, but rather a truncated version. The accelerated approval was based on test results showing higher levels of this micro-dystrophin in muscle cells. The Phase 3 study was intended to show that these higher dystrophin levels translate to improved muscle function.

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In a note sent to investors, William Blair analyst Tim Lugo wrote that the treatment arm performed within management’s expectations, but the placebo group performed better than expected. He added that achieving the main goal at one year is tough in a disease whose progression occurs over the course of 10 years.

Lugo said the current data support the current label covering 4 and 5 year olds as well as likely expansion to boys ages 6 to 7 after FDA review. But expansion to older boys, especially those who are unable to walk, “is more risky because it is hard to say that current data supports this population—though patient groups will obviously be vocal for full approval and there is precedent for most rare disease approvals for broad labels.”

Leerink Partners analyst Joseph Schwartz called the Elevidys Phase 3 data “extremely disappointing,” adding that the results complicate the regulatory path for the gene therapy. He said in a research note that Elevidys’s future prospects rest on the FDA’s willingness to exercise regulatory flexibility—an approach it has previously embraced with other rare disease drug developers, including Sarepta. In 2016, the FDA approved Sarepta’s first Duchenne drug, Exondys 51, an antisense nucleotide that gets a gene to skip over a missing exon to produce a shortened version of the dystrophin protein. That regulatory approval overcame a negative evaluation from FDA reviewers as well as objections from an FDA advisory committee. Sarepta has since won additional approvals for two other exon-skipping therapies.

More recently, regulatory flexibility was shown in amyotrophic lateral sclerosis, where the FDA approved Relyvrio from Amylyx and Qalsody from Biogen . Reata Pharmaceuticals overcame questions about efficacy to win approval for Skyclarys, the first treatment for the ultra-rare neuromuscular disorder Friedreich’s ataxia . Given those affirmative regulatory decisions, Schwartz said it appears the FDA “is willing to work with sponsors and drugs that have less than pristine data packages.”

“Perhaps for any other company, a whiff on the primary endpoint in a Phase 3 would be game over, but [Sarepta] is a special case, especially in a rare neuromuscular disease with a high unmet need like DMD (Duchenne muscular dystrophy),” Schwartz said. “The company has been able to secure accelerated approvals for their three skippers and Elevidys, thus we believe [Sarepta] could also eke out a win here.”

Sarepta said it plans to submit an application to the FDA “as soon as possible” seeking an expansion of Elevidys’s label to encompass the treatment of all Duchenne patients. The company also plans to pursue the regulatory steps needed to transition the gene therapy from accelerated approval to traditional approval. Full results from Elevidys’s Phase 3 study will be shared at future medical meetings and published in a medical journal.

Photo by Sarepta Therapeutics

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An ice loss evaluation of lake-terminating glaciers based on lake bathymetry—a case study of the jiongpu glacier.

1. Introduction

2. materials and methods, 2.1. study region, 2.2. delineation of the glacier and glacial lake, 2.3. bathymetry of the glacial lake, 2.4. dataset of digital elevation models, 2.5. ice loss pattern and spatial classification, 2.6. ice loss calculation in different parts, 3.1. area dynamics and volume investigation of jiongpu co, 3.2. total ice loss of the jiongpu glacier during 2000 to 2020, 4. discussion, 4.1. new volume record with underestimation result of glacial lake, 4.2. ice loss underestimation of the jiongpu glacier, 4.3. limitations and prospects, 5. conclusions, supplementary materials, author contributions, data availability statement, acknowledgments, conflicts of interest.

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Li, D.; Shangguan, D.; Han, T.; Butt, A.Q.; Pan, B.; Cao, B.; Wang, M.; Wang, R.; Li, Y. An Ice Loss Evaluation of Lake-Terminating Glaciers Based on Lake Bathymetry—A Case Study of the Jiongpu Glacier. Remote Sens. 2024 , 16 , 3027. https://doi.org/10.3390/rs16163027

Li D, Shangguan D, Han T, Butt AQ, Pan B, Cao B, Wang M, Wang R, Li Y. An Ice Loss Evaluation of Lake-Terminating Glaciers Based on Lake Bathymetry—A Case Study of the Jiongpu Glacier. Remote Sensing . 2024; 16(16):3027. https://doi.org/10.3390/rs16163027

Li, Da, Donghui Shangguan, Tianding Han, Asim Qayyum Butt, Baotian Pan, Bo Cao, Meixia Wang, Rongjun Wang, and Yaojun Li. 2024. "An Ice Loss Evaluation of Lake-Terminating Glaciers Based on Lake Bathymetry—A Case Study of the Jiongpu Glacier" Remote Sensing 16, no. 16: 3027. https://doi.org/10.3390/rs16163027

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