McKinley A&P 4e Chap010 PPT PDF

Because learning changes everything. ® Chapter 10 Lecture Outline Anatomy & Physiology AN INTEGRATIVE APPROACH Fourth Edition Michael P. McKinley Valerie Dean O’Loughlin Theresa Stouter Bidle Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or...

Because learning changes everything. ® Chapter 10 Lecture Outline Anatomy & Physiology AN INTEGRATIVE APPROACH Fourth Edition Michael P. McKinley Valerie Dean O’Loughlin Theresa Stouter Bidle Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 10.1a Functions of Skeletal Muscle Move the body Move bones, make facial expressions, speak, breathe, swallow Maintain of posture Stabilize joints, maintain body position Protect and support Package internal organs and hold them in place Regulate elimination of materials Circular sphincters control passage of material at orifices Produce heat Help maintain body temperature Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 2 10.1b Characteristics of Skeletal Muscle Tissue Excitability: ability to respond to a stimulus by changing electrical membrane potential Conductivity: involves sending an electrical change down the length of the cell membrane Contractility: exhibited when filaments slide past each other Enables muscle to cause movement Extensibility: ability to be stretched Elasticity: ability to return to original length following a lengthening or shortening Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 3 Section 10.1 What did you learn? 1. What are the five major functions of skeletal muscle? 2. Compare and contrast the skeletal muscle characteristics of contractility, extensibility, and elasticity. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 4 10.2a Gross Anatomy of Skeletal Muscle 1 Each skeletal muscle is an organ Multiple types of tissues working together: skeletal muscle fibers, connective tissue, blood vessels, and nerves Muscle fibers bundled within a fascicle A whole muscle contains many fascicles A fascicle consists of many muscle fibers A muscle fiber is a muscle cell Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 5 10.2a Gross Anatomy of Skeletal Muscle 2 Connective tissue components Three concentric layers of wrapping Epimysium Dense irregular connective tissue wrapping whole muscle Perimysium Dense irregular connective tissue wrapping fascicle Houses many blood vessels and nerves Endomysium Areolar connective tissue wrapping individual fiber Delicate layer for electrical insulation, capillary support, binding of neighboring cells Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 6  Structural Organization of Skeletal Muscle Figure 10.1 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 7 10.2a Gross Anatomy of Skeletal Muscle 3 Connective tissue components (continued) Attachments of muscle to bone (or to skin or to another muscle) can be tendons or aponeuroses Tendon: cordlike structure of dense regular connective tissue Aponeurosis: thin, flattened sheet of dense irregular tissue Deep fascia Dense irregular CT superficial to epimysium Separates individual muscles; binds muscles with similar functions Superficial fascia Areolar and adipose CT superficial to deep fascia Separates muscles from skin Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 8 10.2a Gross Anatomy of Skeletal Muscle 4 Blood vessels and nerves Skeletal is vascularized, has extensive blood vessels Deliver oxygen and nutrients, removing waste products Skeletal muscle is innervated my somatic motor neurons Axons of neurons branch, terminate at neuromuscular junctions Considered voluntary muscle, because contraction is voluntarily controlled Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 9 10.2b Microscopic Anatomy of Skeletal Muscle 1 Parts of a muscle cell (fiber): Sarcoplasm (cytoplasm) Has typical organelles plus contractile proteins and other specializations Multiple nuclei (individual cells are multinucleated) Cell is formed in embryo when multiple myoblasts fuse Some nearby myoblasts become undifferentiated satellite cells for support and repair of muscle fibers Sarcolemma (plasma membrane) Sarcolemma has voltage-gated ion channels that allow for conduction of electrical signals Has T-tubules (transverse tubules) that extend deep into the cell Contain voltage-sensitive calcium channels Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 10  Structure and Organization of a Skeletal Muscle Fiber Figure 10.3a,b Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 11  Sarcolemma and T-tubules Figure 10.3c Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 12 10.2b Microscopic Anatomy of Skeletal Muscle 2 Parts of a muscle cell (continued) Myofibrils (hundreds to thousands per cell) Bundles of myofilaments enclosed in sarcoplasmic reticulum Sarcoplasmic reticulum Internal membrane complex similar to smooth ER Terminal cisternae: blind sacs of sarcoplasmic reticulum Serve as reservoirs for calcium ions Two cisternae with T-tubule in between = triad Contains calcium pumps that import calcium Calcium binds to calmodulin and calsequestrin Contains calcium release channels Triggered by electrical signal traveling down T-tubule; calcium released into sarcoplasm Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 13 10.2b Microscopic Anatomy of Skeletal Muscle 3 Myofilaments are contractile proteins within myofibrils; two types: Thick filaments Consist of bundles of many myosin protein molecules Myosin heads point toward ends of the filament Thin filaments Twisted strands of actin (each F-actin composed of G-actin monomers) G-actin has myosin binding site where myosin heads attach Tropomyosin and troponin are present; regulatory proteins Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 14  Molecular Structure of Thick and Thin Filaments Figure 10.4 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 15 10.2b Microscopic Anatomy of Skeletal Muscle 4 Organization of a sarcomere Myofilaments arranged in repeating units called sarcomeres Composed of overlapping thick and thin filaments Delineated at both ends by Z discs Specialized proteins perpendicular to myofilaments Anchors for thin filaments The positions of thin and thick filaments give rise to alternating I-bands and A-bands Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 16 10.2b Microscopic Anatomy of Skeletal Muscle 5 Organization of a sarcomere (continued) I bands Light-appearing regions that contain only thin filaments Bisected by Z disc Get smaller when muscle contracts (can disappear with maximal contraction) A band Dark-appearing region that contains thick filaments and overlapping thin filaments Contains H zone and M line Makes up central region of sarcomere Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 17  10.2b Microscopic Anatomy of Skeletal Muscle 6 Organization of a sarcomere (continued) H zone: central portion of A band Only thick filaments present; no thin filament overlap Disappears with maximal muscle contraction M line: middle of H zone Protein meshwork structure Attachment site for thick filaments Figure 10.5a Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 18  Structure of a Sarcomere: Longitudinal Section Figure 10.5b Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 19  Structure of a Sarcomere: Cross Sections Figure 10.5c Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 20 10.2b Microscopic Anatomy of Skeletal Muscle 7 Organization of a sarcomere (continued) Other structural and functional proteins Connectin Extends from Z disc to M line Stabilizes thick filaments and has “springlike” properties (passive tension) Dystrophin Anchors some myofibrils to sarcolemma proteins Abnormalities of this protein cause muscular dystrophy Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 21 Clinical View: Muscular Dystrophy Collective term for hereditary diseases where skeletal muscles degenerate Duchenne muscular dystrophy (DMD) is most common type Defective or insufficient dystrophin Sarcolemma damaged during muscle contraction Calcium enters cells, damages proteins Problems begin in early childhood Walking difficulties, muscle atrophy, postural issues Incurable; patients rarely live beyond age 30 Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 22 10.2b Microscopic Anatomy of Skeletal Muscle 8 Mitochondria and other structures associated with energy production Muscle fibers have abundant mitochondria for aerobic ATP production Myoglobin within cells allows storage of oxygen used for aerobic ATP production Glycogen is stored for when fuel is needed quickly Creatinine phosphate can quickly give up its phosphate group to help replenish ATP supply Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 23  10.2c Innervation of Skeletal Muscle Fibers 1 Motor unit: a motor neuron and all the muscle fibers it controls Figure 10.6a Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 24 10.2c Innervation of Skeletal Muscle Fibers 2 Motor unit (continued) Axons of motor neurons from spinal cord (or brain) innervate numerous muscle fibers The number of fibers a neuron innervates varies Small motor units have less than five muscle fibers Allow for precise control of force output Large motor units have thousands of muscle fibers Allow for production of large amount of force (but not precise control) Fibers of a motor unit are dispersed throughout the muscle (not just in one clustered compartment) Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 25  Neuromuscular Junction Location where motor neuron innervates muscle Usually mid-region of muscle fiber Has the following parts: synaptic knob, synaptic cleft, motor end plate Figure 10.7a Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 26 10.2c Innervation of Skeletal Muscle Fibers 3 Neuromuscular junction (continued) Synaptic knob Expanded tip of the motor neuron axon Houses synaptic vesicles Small sacs filled with neurotransmitter acetylcholine (ACh) Has Ca2+ pumps in plasma membrane Establish calcium gradient, with more outside the neuron Has voltage-gated Ca2+ channels in membrane Ca2+ flows into cell (down concentration gradient) if channels open Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 27 10.2c Innervation of Skeletal Muscle Fibers 4 Neuromuscular junction (continued) Motor end plate Specialized region of sarcolemma with numerous folds Has many ACh receptors Plasma membrane protein channels Opened by binding of ACh Allow Na+ entry and K+ exit Synaptic cleft Narrow fluid-filled space Separates synaptic knob from motor end plate Acetylcholinesterase resides here Enzyme that breaks down ACh molecules Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 28  Close-Up of Neuromuscular Junction Figure 10.7b Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 29  10.2d Skeletal Muscle Fibers at Rest Muscle fibers exhibit resting membrane potential (RMP) Fluid inside cell is negative compared to fluid outside cell RMP of muscle cell is about −90 mV RMP established by leak channels and Na+/K+ pumps (voltage-gated channels are closed) Figure 10.8 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 30 Section 10.2 What did you learn? 1 3. Sketch a diagram of a cross section of a muscle, and label the fascicle, muscle fiber, myofibrils, and their associated connective tissue coverings. 4. Draw and label a diagram of a sarcomere. 5. Place the following gross anatomic and microscopic anatomic structures in order from largest to smallest: fascicle, myofibril, myofilament, muscle, muscle fiber, and sarcomere. Describe their anatomic relationship. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 31 Section 10.2 What did you learn? 2 6. Describe a motor unit, and explain why motor units vary in size. 7. Diagram and label the anatomic structures of a neuromuscular junction. 8. Describe the distribution or Na+ and K+ at the sarcolemma. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 32  Overview of Events in Skeletal Muscle Contraction Figure 10.9 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 33 10.3a Neuromuscular Junction: Excitation of a Skeletal Muscle Fiber 1 Calcium entry at synaptic knob Nerve signal travels down axon, opens voltage-gated Ca2+ channels Ca2+ diffuses into synaptic knob Ca2+binds to proteins on surface of synaptic vesicles Release of ACh from synaptic knob Vesicles merge with cell membrane at synaptic knob: exocytosis Thousands of ACh molecules released from about 300 vesicles Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 34  10.3a Neuromuscular Junction: Excitation of a Skeletal Muscle Fiber 2 Binding of ACh at motor end plate ACh diffuses across cleft, binds to receptors, excites fiber Figure 10.10 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 35 Clinical View: Myasthenia Gravis Autoimmune disease, primarily in women Antibodies bind to ACh receptors in neuromuscular junctions Receptors removed from muscle fiber by endocytosis Results in decreased muscle stimulation Rapid fatigue and muscle weakness Eye and facial muscles often involved first May be followed by swallowing problems, limb weakness Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 36  Excitation-Contraction Coupling 1 Stimulation of the fiber is coupled with the sliding of filaments Coupling includes the end-plate potential (EPP), muscle action potential, and release of Ca2+ from the sarcoplasmic reticulum Figure 10.11 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 37 10.3b Sarcolemma, T-tubules, and Sarcoplasmic Reticulum: Excitation-Contraction Coupling 1 End-plate potential (EPP) ACh receptors are chemically gated channels that open when ACh binds to them Na+ diffuses into the cell through the channels (while a little K+ diffuses out) Cell membrane briefly becomes less negative at the end plate region EPP is local but it does lead to the opening of voltage- gated ion channels in the adjacent region of the sarcolemma Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 38 10.3b Sarcolemma, T-tubules, and Sarcoplasmic Reticulum: Excitation-Contraction Coupling 2 Initiation and propagation of action potential along the sarcolemma and T-tubules An action potential (AP) is a rapid rise (depolarization) and fall (repolarization) in the charge of the membrane EPP reaches threshold by causing nearby voltage-gated Na+ channels to open Na+ diffuses into the cell through voltage-gated channels Cell depolarizes: becomes less negative, eventually becomes +30 mV This results in the opening of adjacent voltage-gated Na+ channels and more Na+ entry A chain reaction occurs as depolarization is propagated down the membrane and T-tubules Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 39 10.3b Sarcolemma, T-tubules, and Sarcoplasmic Reticulum: Excitation-Contraction Coupling 3 Initiation and propagation of action potential along the sarcolemma and T-tubules (continued) Just after Na+ channels open, they close and voltage-gated K+ channels open K+ diffuses out of the cell Cell repolarizes: returns to -90mV Repolarization is then propagated down the membrane and T-tubules While the cell is depolarizing and repolarizing it is in a refractory period—unable to respond to another stimulation Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 40  Excitation-Contraction Coupling 2 Figure 10.11 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 41  Events of an Action Potential at the Sarcolemma Figure 10.12 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 42 10.3b Sarcolemma, T-tubules, and Sarcoplasmic Reticulum: Excitation-Contraction Coupling 4 AP travels down T-tubules Causes voltage-sensitive calcium channels in T-tubule membrane to trigger the opening of calcium release channels in SR terminal cisternae Release of Ca2+ from the sarcoplasmic reticulum Ca2+ interacts with myofilaments triggering contraction Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 43 Excitation-Contraction Coupling 3 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 44 10.3c Sarcomere: Crossbridge Cycling 1 The third physiologic event in muscle contraction is the binding of calcium and crossbridge cycling Calcium binding When Ca2+ binds to troponin, it triggers crossbridge cycling Troponin and tropomyosin move so actin is exposed Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 45 10.3c Sarcomere: Crossbridge Cycling 2 Crossbridge cycling: four repeating steps 1) Crossbridge formation Myosin head attaches to exposed binding site on actin 2) Power stroke Myosin head pulls thin filament toward center of sarcomere ADP and Pi released 3) Release of myosin head ATP binds to myosin head causing its release from actin 4) Reset myosin head ATP split into ADP and Pi by myosin ATPase Provides energy to “cock” the myosin head Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 46  10.3c Sarcomere: Crossbridge Cycling 3 Figure 10.13 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 47 10.3c Sarcomere: Crossbridge Cycling 4 Crossbridge cycling (continued) Cycling continues as long as Ca2+ and ATP are present Results in sarcomere shortening as Z discs move closer together Narrowing (or disappearance) of H zone and I band Thick and thin filaments remain the same length but slide past each other Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 48  Sarcomere Shortening (a, b) ©Dr. H. E. Huxley Figure 10.15 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 49 Clinical View: Muscular Paralysis and Neurotoxins Tetanus Spastic paralysis caused by toxin from Clostridium tetani Blocks release of inhibitory neurotransmitter in spinal cord, resulting in overstimulation of muscles Vaccination prevents this life-threatening condition Botulism Muscular paralysis caused by toxin from Clostridium botulinum Prevents release of ACh at synaptic knobs Although toxin ingestion can be life-threatening, careful injections of it can treat spasticity (for example, due to cerebral palsy) or can be used for cosmetic purposes (diminishing wrinkles) Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 50 10.3d Skeletal Muscle Relaxation Events in muscle relaxation Termination of nerve signal and ACh release from motor neuron Hydrolysis of ACh by acetylcholinesterase Closure of ACh receptor causes cessation of end plate potential No further action potential generation Closure of calcium channels in sarcoplasmic reticulum Return of Ca2+ to sarcoplasmic reticulum by pumps Return of troponin to original shape Return of tropomyosin blockade of actin’s myosin binding sites Return of muscle to original position due to its elasticity Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 51 Section 10.3 What did you learn? 1 9. What triggers the binding of synaptic vesicles to the synaptic knob membrane to cause exocytosis of ACh? 10. What two events are linked in the physiologic process called excitation-contraction coupling? 11. Describe the events of excitation-contraction coupling. 12. What is the function of Ca2+ in skeletal muscle contraction? Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 52 Section 10.3 What did you learn? 2 13. Describe the four processes that repeat in crossbridge cycling to cause sarcomere shortening. 14. What causes the release of the myosin head from actin? What resets the myosin head? 15. How do acetylcholinesterase and Ca2+ pumps function in the relaxation of a muscle? Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 53 10.4a Supplying Energy for Skeletal Muscle Metabolism 1 Muscle cells have only a little ATP in storage Stored ATP is spent after about 5 seconds of intense exertion Additional ATP rapidly produced via myokinase Phosphate transferred from one ADP to another to make ATP Three ways to generate additional ATP in skeletal muscle fiber: Creatine phosphate Glycolysis Aerobic cellular respiration Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 54 10.4a Supplying Energy for Skeletal Muscle Metabolism 2 Creatine phosphate Contains a high-energy bond between creatine and phosphate Phosphate can be transferred to ADP to form ATP Catalyzed by creatine kinase 10-15 seconds of additional energy Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 55 10.4a Supplying Energy for Skeletal Muscle Metabolism 3 Glycolysis Does not require oxygen Glucose (from muscle’s glycogen or through blood) is converted to two pyruvate molecules 2 ATP released per glucose molecule Occurs in cytosol Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 56 10.4a Supplying Energy for Skeletal Muscle Metabolism 4 Aerobic cellular respiration Requires oxygen Occurs within mitochondria Pyruvate oxidized to carbon dioxide Transfer of chemical bond energy to NADH and FADH2 Energy used to generate ATP by oxidative phosphorylation Produces a net of 30 ATP Triglycerides can also be used as fuel to produce ATP More ATP from triglycerides with longer fatty acid chains Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 57  Metabolic Processes for Generating ATP Figure 10.17 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 58 10.4a Supplying Energy for Skeletal Muscle Metabolism 5 Lactate formation and its fate Lactate formation from pyruvate occurs under conditions of low oxygen availability Pyruvate converted to lactate by lactate dehydrogenase Lactate can be used as fuel by skeletal muscle fiber or enter blood and taken up by cardiac muscle or liver Lactic acid cycle - cycling of lactate to liver where it’s converted to glucose, and transport of glucose back to muscle Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 59 10.4a Supplying Energy for Skeletal Muscle Metabolism 6 Energy supply and varying intensity of exercise For a sprint (less than 10 seconds) ATP supplied p50-meterrimarily by phosphate transfer system For a 400-meter sprint (less than a minute) ATP supplied primarily by glycolysis after first few seconds For a 1500-meter run (more than a minute) ATP supplied primarily by aerobic processes after first minute Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 60  Utilization of Energy Sources Figure 10.18 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 61 10.4b Oxygen Debt Oxygen debt Amount of additional oxygen needed after exercise to restore pre-exercise conditions Additional oxygen required to Replace oxygen on hemoglobin and myoglobin Replenish glycogen Replenish ATP and creatine phosphate Convert lactic acid back to glucose Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 62 Section 10.4 What did you learn? 16. Additional ATP is made immediately available in skeletal muscle through which phosphate-containing molecules? 17. What are the various means for making ATP available in a 1500-meter race? 18. What is oxygen debt, and how is the additional oxygen used following intense exercise? Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 63 10.5a Criteria for Classification of Skeletal Muscle Fiber Types 1 Skeletal muscle fibers classified based on: 1. Type of contraction generated 2. Means for supplying ATP Type of contraction generated Differences in power, speed, and duration Power related to diameter of muscle fiber Speed and duration related to type of myosin ATPase, quickness of action potential propagation, and quickness of Ca2+ release and reuptake by sarcoplasmic reticulum Fast-twitch fibers are more powerful and have quicker and briefer contractions than slow twitch fibers Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 64 10.5a Criteria for Classification of Skeletal Muscle Fiber Types 2 Means for supplying ATP Oxidative versus glycolytic fibers Oxidative fibers (fatigue-resistant) use aerobic cellular respiration Extensive capillaries, many mitochondria, large supply of myoglobin Red fibers Glycolytic fibers (fatigable) use anaerobic cellular respiration Fewer capillaries, fewer mitochondria, small supply of myoglobin, large glycogen reserves White fibers Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 65 10.5b Classification of Skeletal Muscle Fiber Types Three types of skeletal muscle fibers: 1. Slow oxidative (SO) fibers (type I) Contractions are slower and less powerful High endurance since ATP supplied aerobically About half the diameter of other fibers, red in color due to myoglobin 2. Fast oxidative (FO) fibers (type IIa, intermediate) Contractions are fast and powerful Primarily aerobic respiration, but delivery of oxygen lower Intermediate size, light red in color 3. Fast glycolytic (FG) fibers (type IIx, fast anaerobic) Contractions are fast and powerful Contractions are brief, as ATP production is primarily anaerobic Largest size, white in color due to lack of myoglobin Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 66 10.5c Distribution of Skeletal Muscle Fiber Types A single muscle contains a mixture of fiber types There are variations in proportions of fiber types in different muscle groups Hand muscles have a high percentage of fast glycolytic fibers for quickness Back muscles have a high percentage of slow oxidative fibers to continually maintain postural support Long-distance runners Higher proportion of slow-oxidative fibers in legs Sprinters Higher percentage of fast glycolytic fibers Determined primarily by genes, and partially by training Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 67  Comparison of Fiber Types in Skeletal Muscle Figure 10.19 ©ISM/Medical Images Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 68 Section 10.5 What did you learn? 19. Explain how a fast-twitch fiber differs from a slow-twitch fiber and how an oxidative fiber differs from a glycolytic fiber. 20. Which skeletal muscle fiber type is slow and fatigue- resistant? What is the advantage of this skeletal muscle fiber type? 21. Muscles that maintain posture are composed primarily of what type of skeletal muscle fibers? Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 69  10.6 Muscle Tension in Skeletal Muscle Muscle tension Force generated when a muscle is stimulated to contract Lab experiments measure tension and graph it (myogram) Figure 10.20 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 70 10.6a Muscle Twitch A twitch is a brief contraction to a single stimulus The minimum voltage that triggers a twitch is the threshold Periods of the twitch Latent period Time after stimulus but before contraction begins No change in tension Contraction period Time when tension is increasing Begins as power strokes pull thin filaments Relaxation period Time when tension is decreasing to baseline Begins with release of crossbridges Generally lasts a little longer than contraction period Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 71 10.6b Changes in Stimulus Intensity: Motor Unit Recruitment Muscle is stimulated repeatedly As voltage increases, more units are recruited to contract Recruitment is also called multiple motor unit summation It explains how muscles exhibit varying degrees of force Recruit few motor units to lift pencil vs many to lift suitcase Above a certain voltage, all units are recruited, and so maximum contraction occurs (regardless of how much higher voltage is) Recruitment order based on size of motor units Small first, large last Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 72  Skeletal Muscle Response to Change in Stimulus Intensity Figure 10.21 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 73 10.6c Changes in Stimulus Frequency: Wave Summation, Incomplete Tetany, and Tetany Wave summation (temporal summation) If stimulus frequency set at about 20 per second Relaxation is not completed between twitches Contractile forces add up to produce higher tensions Incomplete tetany and tetany If frequency is increased further, myogram exhibits incomplete tetany Tension increases and twitches partially fuse If frequency is increased further still (for example, 40 to 50 per second), myogram exhibits tetany Tension trace is a smooth line without relaxation High frequency stimuli lead to fatigue (decreased tension production) Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 74  Skeletal Muscle Response to Change in Stimulation Frequency Figure 10.22 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 75 Section 10.6 What did you learn? 22. What events are occurring in a muscle that produce the different components of a muscle twitch (latent period, contraction, and relaxation)? 23. What is recruitment? Explain its importance in the body. 24. What happens to skeletal muscle during wave summation? Explain its importance in the body. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 76 10.7a Muscle Tone Muscle tone Resting tension in a muscle Generated by involuntary nervous stimulation of muscle Some motor units stimulated randomly at any time Change continuously so units not fatigued Do not generate enough tension for movement Decreases during deep sleep Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 77 10.7b Isometric and Isotonic Contractions Isometric contraction Although tension is increased, it is insufficient to overcome resistance Muscle length stays the same For example, holding a weight while arm doesn’t move Isotonic contraction Muscle tension overcomes resistance resulting in movement Tone stays constant, but length changes Concentric contraction Muscle shortens as it contracts For example, in the biceps brachii when lifting a load Eccentric contraction Muscle lengthens as it contracts For example, in the biceps brachii when lowering a load Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 78  Isometric Versus Isotonic Contraction Figure 10.23 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 79  Muscle Length and Tension Relationship During Muscle Contraction Figure 10.24 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 80 Clinical View: Isometric Contraction and Increase in Blood Pressure Sustained isometric contractions Associated with increase in blood pressure May be a concern for those with baseline high blood pressure For example, shoveling snow General peripheral constriction (from cold) elevates pressure Isometric contractions of shoveling also increase pressure Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 81 10.7c Length-Tension Relationship The tension a muscle produces depends on its length at the time of stimulation Fiber at resting length generates maximum contractile force Optimal overlap of thick and thin filaments Fiber at a shortened length generates weaker force Filament movement is limited (already close to Z disc) Fiber at an extended length generates weaker force Minimal thick and thin filament overlap for crossbridge formation Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 82  Length-Tension Curve Figure 10.25 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 83 10.7d Muscle Fatigue Muscle fatigue: reduced ability to produce muscle tension Primarily caused by a decrease in glycogen stores during prolonged exercise Other possible causes of fatigue Excitation at neuromuscular junction Insufficient Ca2+ to enter synaptic knob Decreased number of synaptic vesicles Excitation-contraction coupling Altered ion concentrations impair action potential conduction and Ca2+ release from sarcoplasmic reticulum Crossbridge cycling Excessive Pi slows release of Pi from myosin head Less Ca2+ available for troponin (some Ca2+ is bound to Pi) Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 84 Section 10.7 What did you learn? 25. Explain the function of skeletal muscle tone. 26. When you flex your biceps brachii while doing “biceps curls,” what is the type of muscle contraction – is it an isometric contraction or an isotonic contraction? 27. Describe the relative force of contraction that can be developed in your back muscles when you bend at the knees to lift an object and when you bend at the waist to lift an object, based on the length-tension relationship. Explain the significance. 28. How can muscle fatigue result from changes in each of the three primary events of skeletal muscle contraction? Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 85 10.8a Effects of Exercise Changes in muscle from a sustained exercise program Endurance exercise leads to better ATP production (for example, more mitochondria) Resistance exercise leads to hypertrophy Muscle increases in size due to increases in synthesis of contractile proteins Muscle also increases glycogen reserves and mitochondria Limited amount of hyperplasia (increase in number of fibers) Changes in muscle from lack of exercise Atrophy: decrease in size due to lack of use For example, someone wearing a cast Initially reversible, but becomes permanent if extreme Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 86 10.8b Effects of Aging Loss of muscle mass with age Slow loss begins in person’s mid-30s due to decrease in activity Decreased size, power, and endurance of skeletal muscle Loss in fiber number and diameter (decrease in myofibrils) Decreased oxygen storage capacity Decreased circulatory supply to muscles with exercise Reduced capacity to recover from injury Decreased number of satellite cells Fibrosis: muscle mass often replaced by dense regular connective tissue Decreased flexibility Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 87 Clinical View: Anabolic Steroids as Performance- Enhancing Compounds Anabolic steroids Synthetic substances that mimic testosterone Require prescription for legal use Stimulate manufacture of muscle proteins Popular performance enhancers Side effects include Increased risk of heart disease and stroke Kidney damage and liver tumors Testicular atrophy, breast development in males Acne, high blood pressure, aggressive behavior Growth of facial hair and menstrual irregularities in women Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 88 Section 10.8 What did you learn? 29. What anatomic changes occur in a skeletal muscle fiber when it undergoes hypertrophy? 30. What changes in skeletal muscle occur as a result of aging? Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 89 10.9 Cardiac Muscle Tissue Cardiac muscle cells Short, branching fibers One or two nuclei Striated (contain sarcomeres) Many mitochondria—use aerobic respiration Intercalated discs join ends of neighboring fibers Discs contain desmosomes and gap junctions Contractions started by heart’s autorhythmic pacemaker cells Heart rate and contraction force influenced by autonomic nervous system Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 90  Cardiac Muscle Figure 10.27 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 91 Section 10.9 What did you learn? 31. What are three anatomic or physiologic differences between skeletal muscle and cardiac muscle? Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 92 10.10a Location of Smooth Muscle Smooth muscle is found in a variety of organ systems with a variety of roles Examples: In blood vessels of cardiovascular system Helps regulate blood pressure and flow In bronchioles of respiratory system Controls airflow to alveoli In intestines of digestive system Mixes and propels materials In ureters of urinary system Propels urine from kidneys to bladder In uterus of female reproductive system Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 93  Location of Smooth Muscle (blood vessel) ©McGraw-Hill Education/Christine Eckel; (bronchiole) ©MicroScape/Science Source; (large intestine) ©Victor P. Eroschenko; (urinary bladder) ©McGraw-Hill Education/Al Telser; (uterus) ©MicroScape/Science Source Figure 10.28 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 94 10.10b Microscopic Anatomy of Smooth Muscle 1 Smooth muscle cells have fusiform shape Wide in the middle with tapered ends Smaller than skeletal muscle fibers Sarcolemma has varied types of Ca2+ channels (gated by chemicals, voltage, etc.) Transverse tubules absent Surface area increased by caveolae (flasklike invaginations) Sarcoplasmic reticulum sparse Outside of cell is important source of Ca2+ Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 95  Microscopic Anatomy of Smooth Muscle Figure 10.29 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 96 10.10b Microscopic Anatomy of Smooth Muscle 2 Arrangement of anchoring proteins and contractile proteins of smooth muscle Cytoskeleton composed of extensive intermediate filaments Dense bodies: points where intermediate filaments interact within sarcoplasm Dense plaques: points where intermediate filaments attach on inner sarcolemma Contractile proteins Arranged between dense bodies and dense plaques Oriented at oblique angles to longitudinal axis of cell Contraction causes a twisting motion Lack sarcomeres and Z discs (smooth = no striations) Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 97 10.10b Microscopic Anatomy of Smooth Muscle 3 Like skeletal muscle, smooth muscle filaments have actin, myosin, and troponin Unlike skeletal muscle, smooth muscle Filaments have myosin heads along their entire length; can form additional cross bridges Filaments can perform the latchbridge mechanism: myosin attaches to actin for extended time without using extra ATP Has calmodulin: protein that binds Ca2+ to trigger contraction Has myosin light-chain kinase (MLCK): enzyme that phosphorylates myosin heads when activated by calmodulin Has myosin light-chain phosphatase: enzyme that dephosphorylates myosin head (required for relaxation) Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 98  Smooth Muscle Contraction Figure 10.30 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 99 10.10c Smooth Muscle Contraction 1 Steps of contraction Stimulus leads to opening of voltage-gated Ca2+ channels Ca2+ enters sarcoplasm and binds to calmodulin Calcium-calmodulin complex binds to myosin light-chain kinase (MLCK) MLCK phosphorylates myosin head Crossbridges form, pull on actin, similar to skeletal muscle but more slowly As thin filament slides, it pulls on dense bodies Dense bodies attached to intermediate filaments, which are attached to dense plaques in sarcolemma These filaments move inward, entire cell shortens Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 100 10.10c Smooth Muscle Contraction 2 Relaxation of smooth muscle Cessation of stimulation Removal of Ca2+ from sarcoplasm Dephosphorylation of myosin by myosin light-chain phosphatase Can be slow to relax due to latchbridge mechanism Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 101 10.10c Smooth Muscle Contraction 3 Smooth muscle contraction characteristics Long latent period Takes time to phosphorylate myosin head Slow ATPase activity Long duration Slow calcium pumps Need for dephosphorylation of myosin head Latchbridge mechanism Slowness fits its functional requirements Extended contractions maintain continuous tone For example, in walls of blood vessels Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 102 10.10c Smooth Muscle Contraction 4 Smooth muscle contraction characteristics (continued) Fatigue-resistant Energy requirements low compared to skeletal muscle Can maintain contraction without ATP through latchbridge mechanism Broad length-tension curve Lacks limitations because no Z discs Myosin heads present in center of thick filaments Can contract forcefully, even when 50% to 200% of resting length For example, allows emptying bladder regardless of amount of urine Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 103 10.10d Controlling Smooth Muscle Control of smooth muscle Autonomic (involuntary) nervous system secretes transmitters Muscle’s response depends on neurotransmitter present and muscle’s receptor for it For example, smooth muscle of bronchioles contracts in response to ACh and relaxes in response to norepinephrine Response to stretch Myogenic response is contraction in reaction to stretch Stress-relaxation response is relaxation after prolonged stretch Other stimulating factors include: Various hormones, low pH, low O2, high CO2, certain drugs, pacemaker cells Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 104 10.10e Functional Categories of Smooth Muscle 1 Two categories of smooth muscle: multiunit and single unit Multiunit smooth muscle Arranged in units that receive stimulation to contract individually Found in Iris and ciliary muscles of the eye Arrector pili muscles in skin Larger air passageways in respiratory system Walls of larger arteries Degree of contraction depends on number of motor units activated, similar to skeletal muscle Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 105 10.10e Functional Categories of Smooth Muscle 2 Single-unit (visceral) smooth muscle Most common type Stimulated to contract in unison as cells linked by gap junctions Form two or three sheets in wall of hollow organ Locations include Walls of digestive, urinary, and reproductive tracts Portions of respiratory tract Most blood vessels Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 106 10.10e Functional Categories of Smooth Muscle 3 Stimulation of single-unit smooth muscle Occurs through varicosities—swellings of autonomic neurons Varicosities contain synaptic vessels with one type of neurotransmitter Either ACh or norepinephrine Receptors scattered across the sarcolemma Diffuse junctions Numerous smooth muscle cells stimulated simultaneously Stimulation spread from cell to cell via gap junctions so contraction is synchronous Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 107  Multiunit and Single-Unit Smooth Muscle Figure 10.31 Access the text alternative for slide images. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 108 Section 10.10 What did you learn? 1 32. Where is smooth muscle located in the human body? 33. How are anchoring proteins and contractile proteins in smooth muscle cells arranged 34. What is the specific role of the following structures within smooth muscle cells: calmodulin, myosin light-chain kinase, and myosin light-chain phosphatase? 35. What are the steps of smooth muscle contraction? Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 109 Section 10.10 What did you learn? 2 36. What unique characteristics of smooth muscle allow it to fulfill its functions? Explain. 37. What are the various forms of stimulation for controlling smooth muscle? 38. Explain the stress-relaxation response of smooth muscle. 39. Explain why smooth muscle of the eye is multiunit smooth muscle and the smooth muscle in the wall of digestive organs is single-unit smooth muscle. Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 110  End of Main Content Because learning changes everything. ® www.mheducation.com Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.