Vander, Sherman, Luciano's Human Physiology -The Mechanisms of Body Function

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Mean Motor Unit Forces: • FF motor units get smaller in old age and decrease in number • S motor units get bigger with no change in number • Decreased rate of force generation and POWER!! 225 200 Adult 175 Old 150 125 Maximum Isometric Force (mN) 100 75 50 25 0 FF FI FR S Kadhiresan et al., (1996) J Physiol 493:543-552. Motor Unit Classification Vander's Human Physiology, Twelfth Edition, carries on the tradition of clarity and accuracy, while refining and updating the content to meet the needs of today's instructors and students. The twelfth edition features a streamlined, clinically oriented focus to the study of human body systems. It has also responded to reviewer requests for more clinical applications. Chapter 19 was new for the eleventh edition, with three complete case studies. The twelfth edition will contain an additional new case study. Additional Physiology Inquiries have been added to many figures throughout the chapters. These critical-thinking questions are just one more opportunity to add to the student's learning experience. Most likely to cause muscle injury Three potential actions during muscle contraction: (Isotonic: shortening against fixed load, speed dependent on M·ATPase activity and load) Biceps muscle shortens during contraction • shortening • isometric • lengthening Biceps muscle lengthens during contraction Modified from Vander, Sherman, Luciano Human Physiology, McGraw-Hill. Muscular Dystrophy: A frequently fatal disease of muscle deterioration • Muscular dystrophies have in the past been classified based on subjective and sometimes • subtle differences in clinical presentation, such as age of onset, involvement of particular • muscles, rate of progression of pathology, mode of inheritance. • Since the discovery of dystrophin, numerous genetic disease loci have been linked to protein • products and to cellular phenotypes, generating models for studying the pathogenesis of the • dystrophies. • Proteins localized in the nucleus, cytosol, cytoskeleton, sarcolemma, and ECM. Cohn and Campbell (2000) Muscle Nerve 23:1459-1471. Shortening velocity dependent on ATPase activity Different myosin heavy chains (MHCs) have different ATPase activities. There are at least 7 separate skeletal muscle MHC genes…arranged in series on chromosome 17. Two cardiac MHC genes located in tandem on chromosome 14. The slow b cardiac MHC is the predominant gene expressed in slow fibers of mammals. Goldspink (1999) J Anat 194:323-334.

Structural hierarchy of skeletal muscle Muscle A little less than half of the body’s mass is composed of skeletal muscle, with most muscles linked to bones by tendons through which the forces and movements developed during contractions are transmitted to the skeleton. Muscle fibers Muscle fiber Myofibril Sarcomere Modified from McMahon, Muscles, Reflexes and Locomotion Princeton University Press, 1984. Disuse causes atrophy -- USE IT OR LOSE IT! Individual fiber atrophy (loss of myofibrils) with no loss in fibers. Effect more pronounced in Type II fibers. “Completely reversible” (in young healthy individuals). ATPase activity: Type I fibers light Type II fibers dark Control Prolonged bed rest Images courtesy of John FaulknerEric Widmaier (Boston University), Hershel Raff (Medical College of Wisconsin), and Kevin Strang (University of Wisconsin) have taken on the challenge of maintaining the strengths and reputation of Vander's Human Physiology: The Mechanisms of Body Function. Moving beyond the listing of mere facts, it stresses the causal chains of events that constitute the mechanisms of body function. The fundamental purpose of this textbook is to present the principles and facts of human physiology in a format that is Vander's Human Physiology, thirteenth edition, carries on the tradition of clarity and accuracy, while refining and updating the content to meet the needs of today's instructors and students. The thirteenth edition features a streamlined, clinically oriented focus to the study of human body systems. It has also responded to reviewer requests for more clinical applications. Physiology Inquiries are maintained throughout the chapters. These critical-thinking questions associated with figures are just one more opportunity to add to the student's learning experience. Chemomechanical coupling – conversion of chemical energy (ATP about 7 kcal/mole) into force/movement. • ATP is unstable thermodynamically • Two most energetically favorable steps: • 1. ATP binding to myosin • 2. Phosphate release from myosin • Rate of cycling determined by M·ATPase activity and external load Adapted from Goldman & Brenner (1987) Ann Rev Physiol 49:629-636. weeks post * p < 0.05 * * A single prior exposure to a protocol of lengthening contractions reduced the force deficit and damaged fibers 60% non-trained 50 40 30 20 10 0 Force Deficit (% control) Injured Fibers (% total) Koh & Brooks (2001) Am J Physiol 281:R155-R161.

Ghost” fiber 3 days after initial injury Faulkner, Brooks and Zerba (1995) J Gerontol 50:B124-B129. Power output: the most physiologically relevant marker of performance Power = work / time = force x distance / time = force x velocity Peak power obtained at intermediate loads and intermediate velocities. Figure from Berne and Levy, Physiology Mosby—Year Book, Inc., 1993. Performance Declines with Aging --despite maintenance of physical activity 100 80 60 Performance (% of peak) 40 Shotput/Discus Marathon 20 Basketball (rebounds/game) 0 20 30 40 50 60 10 Age (years) D.H. Moore (1975) Nature 253:264-265. NBA Register, 1992-1993 EditionNumber of motor units declines during aging - extensor digitorum brevis muscle of human beings AGE-ASSOCIATED ATROPHY DUE TO BOTH… Individual fiber atrophy (which may be at least partially preventable and reversible through exercise). Loss of fibers (which as yet appears irreversible). Campbell et al., (1973) J Neurol Neurosurg Psych 36:74-182. Increased use: strength training Early gains in strength appear to be predominantly due to neural factors…optimizing recruitment patterns. Long term gains almost solely the result of hypertrophy i.e. increased size. Motor unit remodeling with aging Central nervous system Muscle Motor neuron loss AGING • Fewer motor units • More fibers/motor unit Degeneration-regeneration not necessary to provide muscles protection from contraction-induced injury non-trained trained passive trained isometric *different from non- -trained (p<0.05) * * Force deficit (% control) Injured fibers (% total) * Koh & Brooks (2001) Am J Physiol 281:R155-R161. Force deficit Injured fibers • Despite the increase in susceptibility to injury with aging, • and the decreased ability to recover, muscles in old • animals can be conditioned for protection from injury. • Maintenance of conditioned fibers, particularly in muscles • of elderly people, may prevent inadvertent damage during • contractions.

The Online Learning Center is designed to enhance your learning. Book-specific content such as quizzing, case studies, objectives, and web links can all be accessed by choosing from the list to the left. These materials are designed to help you succeed in your course. Homeostasis: A Framework for Human Physiology Chemical Composition of the Body Cellular structure, proteins, and Metabolism Movement of Molecules Across Cell Membranes Control of Cells by Chemical Messengers Neuronal Signaling and the Structure of the Nervous System Sensory Physiology Consciousness, the Brain, and Behavior Muscle Control of Body Movement The Endocrine System Cardiovascular Physiology Respiratory Physiology The Kidneys and Regulation of Water and Inorganic Ions The Digestion and Absorption of Food Regulation of Organic Metabolism and Energy Balance Reproduction Defense Mechanisms of the Body Medical Physiology: Integration Using Clinical Cases. Continuum of Physical Activity strength trained endurance trained Load controls inactivity Frequency of recruitment Muscle is plastic! Muscle “adapts” to meet the habitual level of demand placed on it, i.e. level of physical activity. Level of physical activity determined by the frequency of recruit- ment and the load. Increase muscle use – endurance training – strength training (cannot be optimally trained for both strength and endurance) Decrease muscle use – prolonged bed rest –limb casting –denervation –space flight. Adapted from Faulkner, Green and White In: Physical Activity, Fitness, and Health,Ed. Bouchard, Shephard and Stephens Human Kinetics Publishers, 1994Microstructure Modified from Squire, Muscle: Design, Diversity, and Disease Benjamin/Cummings, 1986 Originally from Lazarides (1980) Nature 283:249-256. Here's a quote from new lead author Eric Widmaier about the team's plans for the future of the Vander text... Only lengthening contractions result in damaged fibers * control 20 passive isometric lengthening * different from zero (p<0.05) 15 Injured fibers (% total) 10 5 0 Other Measures of Contraction-Induced Injury • immediate mechanical disruption observed by EM. • enzyme release from degenerating muscle fibers • in human beings, subjective reports of muscle soreness • in the absence of fatigue, a decrease in the development of force Koh & Brooks (2001) Am J Physiol 281:R155-R161. Calcineurin is a Ca2+-regulated • serine/threonine phosphatase. • Caclineurin dephosphorylates nuclear factor of activated T cells (NFAT) transcription factors. • Dephosphorylated NFATs • translocate to the nucleus where • combinatorially with other factors they activate transcription. • A second target of calcineurin is the transcriptional co-activator, peroxisome-proliferator-activated receptor-g co-activator-1 (PGC-1a). • Activation of calcineurin in skeletal myocytes selectively up-regulates slow-fiber-specific gene promoters and the effect enhanced with PGC-1a expression • PGC-1a activates mitochondrial biogenesis. A calcineurin dependent transcriptional pathway appears to control skeletal muscle fiber type. Lin et al. (2002) Nature 418:797-801 But first, we should explain that the current authors (Art Vander, James Sherman and Dorothy Luciano) are still very much alive, and well. They are simply ready to retire from authoring the text-- which presents us with an opportunity to bring in a fantastic new team to continue the success of the text! The original author team will still be involved in future editions and will continue to serve as "consultants" on their book.

In 1970, Drs. Vander, Sherman and Luciano created what has long been regarded by many as the most complete, readable and up-to-date Human Physiology textbook in the world. I am honored and thrilled to take over the reigns of this wonderful textbook, as it moves into the rapidly expanding realm of 21st century physiology. Together with my outstanding co-authors, Dr. Hershel Raff and Dr. Kevin Strang, we eagerly look towards the future with the goal of continuing our predecessors' standards of excellence, while making the text even more attractive to the ever-widening audience of physiology students." Endurance training Little hypertrophy but major biochemical adaptations within muscle fibers. Increased numbers of mitochondria; concentration and activities of oxidative enzymes (e.g. succinate dehydrogenase, see below). Succinate dehy- drogenase (SDH) activity: Low activity light High activity dark Control 12-weeks treadmill running Images courtesy of John Faulkner and Timothy White Muscle injury may play a role in the development of atrophy with aging. • Muscles in old animals are more susceptible to contraction- • induced injury than those in young or adult animals. • Muscles in old animals show delayed and impaired recovery • following contraction-induced injury. • Following severe injury, muscles in old animals display • prolonged, possibly irreversible, structural and functional • deficits.

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