Muscle Physiology PDF

Muscles Animals use muscles to convert the chemical energy of ATP into mechanical work. Three different kinds of muscles are found in vertebrate animals  He...

Muscles Animals use muscles to convert the chemical energy of ATP into mechanical work. Three different kinds of muscles are found in vertebrate animals  Heart muscle — also called cardiac muscle — makes up the wall of the heart. Throughout life, it contracts some 70 times per minute pumping about 5 liters of blood each minute.  Smooth muscle is found in the walls of all the hollow organs of the body (except the heart). Its contraction reduces the size of these structures. Thus it: o regulates the flow of blood in the arteries o moves your breakfast along through your gastrointestinal tract o expels urine from your urinary bladder o sends babies out into the world from the uterus o regulates the flow of air through the lungs The contraction of smooth muscle is generally not under voluntary control.  Skeletal muscle, as its name implies, is the muscle attached to the skeleton. It is also called striated muscle. The contraction of skeletal muscle is under voluntary control. Anatomy of Skeletal Muscle A single skeletal muscle, such as the triceps muscle, is attached at its  origin to a large area of bone; in this case, the humerus  At its other end, the insertion, it tapers into a glistening white tendon which, in this case, is attached to the ulna, one of the bones of the lower arm. As the triceps contracts, the insertion is pulled toward the origin and the arm is straightened or extended at the elbow. Thus the triceps is an extensor. Because skeletal muscle exerts force only when it contracts, a second muscle — a flexor — is needed to flex or bend the joint. The biceps muscle is the flexor of the lower arm. Together, the biceps and triceps make up an antagonistic pair of muscles. Similar pairs, working antagonistically across other joints, provide for almost all the movement of the skeleton. The Muscle Fiber Skeletal muscle is made up of thousands of cylindrical muscle fibers often running all the way from origin to insertion. The fibers are bound together by connective tissue through which run blood vessels and nerves. Each muscle fibers contains:  an array of myofibrils that are stacked lengthwise and run the entire length of the fiber.  mitochondria  an extensive smooth endoplasmic reticulum (SER)  many nuclei. The multiple nuclei arise from the fact that each muscle fiber develops from the fusion of many cells (called myoblasts). The number of fibers is probably fixed early in life. This is regulated by myostatin, a cytokine that is synthesized in muscle cells (and circulates as a hormone later in life). Myostatin suppresses skeletal muscle development. Cattle and mice with inactivating mutations in their myostatin genes develop much larger muscles. Some athletes and other remarkably strong people have been found to carry one mutant myostatin gene. These discoveries have already led to the growth of an illicit market in drugs supposedly able to suppress myostatin.  In adults, increased strength and muscle mass comes about through an increase in the thickness of the individual fibers and increase in the amount of connective tissue. In the mouse, at least, fibers increase in size by attracting more myoblasts to fuse with them. The fibers attract more myoblasts by releasing the cytokine interleukin 4 (IL-4). Anything that lowers the level of myostatin also leads to an increase in fiber size. Because a muscle fiber is not a single cell, its parts are often given special names such as:  sarcolemma for plasma membrane  sarcoplasmic reticulum for endoplasmic reticulum  sarcosome for mitochondrion  sarcoplasm for cytoplasm although this tends to obscure the essential similarity in structure and function of these structures and those found in other cells. The  nuclei and mitochondria are located just beneath the plasma membrane  the endoplasmic reticulum extends between the myofibrils. Seen from the side under the microscope, skeletal muscle fibers show a pattern of cross banding, which gives rise to the other name: striated muscle. The striated appearance of the muscle fiber is created by a pattern of alternating  dark A bands and  light I bands.  The A bands are bisected by the H zone  The I bands are bisected by the Z line. Each myofibril is made up of arrays of parallel filaments.  The thick filaments have a diameter of about 15 nm. They are composed of the protein myosin.  The thin filaments have a diameter of about 5 nm. They are composed chiefly of the protein actin along with smaller amounts of two other proteins: o troponin and o tropomyosin. The anatomy of a sarcomere  The thick filaments produce the dark A band.  The thin filaments extend in each direction from the Z line. Where they do not overlap the thick filaments, they create the light I band.  The H zone is that portion of the A band where the thick and thin filaments do not overlap.  The entire array of thick and thin filaments between the Z lines is called a sarcomere. Shortening of the sarcomeres in a myofibril produces the shortening of the myofibril and, in turn, of the muscle fiber of which it is a part. Activation of Skeletal Muscle The contraction of skeletal muscle is controlled by the nervous system. The Dying Lioness (an Assyrian relief dating from about 650 B.C. and supplied through the courtesy of The Trustees of the British Museum) shows this vividly. Injury to the spinal cord has paralyzed the otherwise undamaged hind legs. In this respect, skeletal muscle differs from smooth and cardiac muscle. Both cardiac and smooth muscle can contract without being stimulated by the nervous system. Nerves of the autonomic branch of the nervous system lead to both smooth and cardiac muscle, but their effect is one of moderating the rate and/or strength of contraction. The Neuromuscular Junction Nerve impulses (action potentials) traveling down the motor neurons of the sensory-somatic branch of the nervous system cause the skeletal muscle fibers at which they terminate to contract. The junction between the terminal of a motor neuron and a muscle fiber is called the neuromuscular junction. It is simply one kind of synapse. (The neuromuscular junction is also called the myoneural junction.) The terminals of motor axons contain thousands of vesicles filled with acetylcholine (ACh). When an action potential reaches the axon terminal, hundreds of these vesicles discharge their ACh onto a specialized area of postsynaptic membrane on the fiber. This area contains a cluster of transmembrane channels that are opened by ACh and let sodium ions (Na+) diffuse in. The interior of a resting muscle fiber has a resting potential of about −95 mV. The influx of sodium ions reduces the charge, creating an end plate potential. If the end plate potential reaches the threshold voltage (approximately −50 mV), sodium ions flow in with a rush and an action potential is created in the fiber. The action potential sweeps down the length of the fiber just as it does in an axon. No visible change occurs in the muscle fiber during (and immediately following) the action potential. This period, called the latent period, lasts from 3–10 msec. Before the latent period is over,  the enzyme acetylcholinesterase o breaks down the ACh in the neuromuscular junction (at a speed of 25,000 molecules per second) o the sodium channels close, and o the field is cleared for the arrival of another nerve impulse.  the resting potential of the fiber is restored by an outflow of potassium ions The brief (1–2 msec) period needed to restore the resting potential is called the refractory period. Tetanus The process of contracting takes some 50 msec; relaxation of the fiber takes another 50–100 msec. Because the refractory period is so much shorter than the time needed for contraction and relaxation, the fiber can be maintained in the contracted state so long as it is stimulated frequently enough (e.g., 50 stimuli per second). Such sustained contraction is called tetanus. In the figure,  When shocks are given at 1/sec, the muscle responds with a single twitch.  At 5/sec and 10/sec, the individual twitches begin to fuse together, a phenomenon called clonus.  At 50 shocks per second, the muscle goes into the smooth, sustained contraction of tetanus. Clonus and tetanus are possible because the refractory period is much briefer than the time needed to complete a cycle of contraction and relaxation. Note that the amount of contraction is greater in clonus and tetanus than in a single twitch. As we normally use our muscles, the individual fibers go into tetanus for brief periods rather than simply undergoing single twitches. The Sliding-Filament Model Each molecule of myosin in the thick filaments contains a globular subunit called the myosin head. The myosin heads have binding sites for  the actin molecules in the thin filaments and  ATP Activation of the muscle fiber causes the myosin heads to bind to actin. An allosteric change occurs which draws the thin filament a short distance (~10 nm) past the thick filament. Then the linkages break (for which ATP is needed) and reform farther along the thin filament to repeat the process. As a result, the filaments are pulled past each other in a ratchetlike action. There is no shortening, thickening, or folding of the individual filaments. As a muscle contracts,  the Z lines come closer together  the width of the I bands decreases  the width of the H zones decreases, but  there is no change in the width of the A band. Conversely, as a muscle is stretched,  the width of the I bands and H zones increases,  but there is still no change in the width of the A band. Coupling Excitation to Contraction Calcium ions (Ca2+) link action potentials in a muscle fiber to contraction.  In resting muscle fibers, Ca2+ is stored in the endoplasmic (sarcoplasmic)  reticulum.  Spaced along the plasma membrane (sarcolemma) of the muscle fiber are inpocketings of the membrane that form tubules of the "T system". These tubules plunge repeatedly into the interior of the fiber.  The tubules of the T system terminate near the calcium-filled sacs of the sarcoplasmic reticulum.  Each action potential created at the neuromuscular junction sweeps quickly along the sarcolemma and is carried into the T system.  The arrival of the action potential at the ends of the T system triggers the release of Ca2+.  The Ca2+ diffuses among the thick and thin filaments where it  binds to troponin on the thin filaments.  This turns on the interaction between actin and myosin and the sarcomere contracts.  Because of the speed of the action potential (milliseconds), the action potential arrives virtually simultaneously at the ends of all the tubules of the T system, ensuring that all sarcomeres contract in unison.  When the process is over, the calcium is pumped back into the sarcoplasmic reticulum using a Ca2+ ATPase]. Isotonic versus Isometric Contractions If a stimulated muscle is held so that it cannot shorten, it simply exerts tension. This is called an isometric ("same length") contraction. If the muscle is allowed to shorten, the contraction is called isotonic ("same tension"). Motor Units All motor neurons leading to skeletal muscles have branching axons, each of which terminates in a neuromuscular junction with a single muscle fiber. Nerve impulses passing down a single motor neuron will thus trigger contraction in all the muscle fibers at which the branches of that neuron terminate. This minimum unit of contraction is called the motor unit. The size of the motor unit is small in muscles over which we have precise control. Examples:  a single motor neuron triggers fewer than 10 fibers in the muscles controlling eye movements   the motor units of the muscles controlling the larynx are as small as 2–3 fibers per motor neuron  In contrast, a single motor unit for a muscle like the gastrocnemius (calf) muscle may include 1000–2000 fibers (scattered uniformly through the muscle). Although the response of a motor unit is all-or-none, the strength of the response of the entire muscle is determined by the number of motor units activated. Even at rest, most of our skeletal muscles are in a state of partial contraction called tonus. Tonus is maintained by the activation of a few motor units at all times even in resting muscle. As one set of motor units relaxes, another set takes over. Fueling Muscle Contraction ATP is the immediate source of energy for muscle contraction. Although a muscle fiber contains only enough ATP to power a few twitches, its ATP "pool" is replenished as needed. There are three sources of high-energy phosphate to keep the ATP pool filled.  creatine phosphate  glycogen  cellular respiration in the mitochondria of the fibers. Creatine phosphate The phosphate group in creatine phosphate is attached by a "high-energy" bond like that in ATP. Creatine phosphate derives its high-energy phosphate from ATP and can donate it back to ADP to form ATP. Creatine phosphate + ADP ↔ creatine + ATP The pool of creatine phosphate in the fiber is about 10 times larger than that of ATP and thus serves as a modest reservoir of ATP. Glycogen Skeletal muscle fibers contain about 1% glycogen. The muscle fiber can degrade this glycogen by glycogenolysis producing glucose-1-phosphate. This enters the glycolytic pathway to yield two molecules of ATP for each pair of lactic acid molecules produced. Not much, but enough to keep the muscle functioning if it fails to receive sufficient oxygen to meet its ATP needs by respiration. However, this source is limited and eventually the muscle must depend on cellular respiration. Cellular respiration Cellular respiration not only is required to meet the ATP needs of a muscle engaged in prolonged activity (thus causing more rapid and deeper breathing), but is also required afterwards to enable the body to resynthesize glycogen from the lactic acid produced earlier (deep breathing continues for a time after exercise is stopped). The body must repay its oxygen debt. Type I vs. Type II Fibers Two different types of muscle fiber can be found in most skeletal muscles. The Type I and Type II fibers differ in their structure and biochemistry. Type I Fibers  loaded with mitochondria and  depend on cellular respiration for ATP production  resistant to fatigue  rich in myoglobin and hence red in color  activated by small-diameter, thus slow-conducting, motor neurons  also known as "slow-twitch" fibers  dominant in muscles that depend on tonus, e.g., those responsible for posture Type II Fibers  few mitochondria  rich in glycogen and  depend on glycolysis for ATP production  fatigue easily  low in myoglobin hence whitish in color  activated by large-diameter, thus fast-conducting, motor neurons  also known as "fast-twitch" fibers  dominant in muscles used for rapid movement Most skeletal muscles contain some mixture of Type I and Type II fibers, but a single motor unit always contains one type or the other, never both. The ratio of Type I and Type II fibers can be changed by endurance training (producing more Type I fibers). Cardiac Muscle Cardiac or heart muscle resembles skeletal muscle in some ways: it is striated and each cell contains sarcomeres with sliding filaments of actin and myosin. However, cardiac muscle has a number of unique features that reflect its function of pumping blood.  The myofibrils of each cell (and cardiac muscle is made of single cells — each with a single nucleus) are branched.  The branches interlock with those of adjacent fibers by adherens junctions. These strong junctions enable the heart to contract forcefully without ripping the fibers apart.  The action potential that triggers the heartbeat is generated within the heart itself. Motor nerves (of the autonomic nervous system) do run to the heart, but their effect is simply to modulate — increase or decrease — the intrinsic rate and the strength of the heartbeat. Even if the nerves are destroyed (as they are in a transplanted heart), the heart continues to beat.  The action potential that drives contraction of the heart passes from fiber to fiber through gap junctions. o Significance: All the fibers contract in a synchronous wave that sweeps from the atria down through the ventricles and pumps blood out of the heart. Anything that interferes with this synchronous wave (such as damage to part of the heart muscle from a heart attack) may cause the fibers of the heart to beat at random — called fibrillation. Fibrillation is the ultimate cause of most deaths and its reversal is the function of defibrillators that are part of the equipment in ambulances, hospital emergency rooms, and — recently — even on U.S. air lines.  The refractory period in heart muscle is longer than the period it takes for the  muscle to contract (systole) and relax (diastole). Thus tetanus is not possible (a good thing, too!).  Cardiac muscle has a much richer supply of mitochondria than skeletal muscle. This reflects its greater dependence on cellular respiration for ATP.  Cardiac muscle has little glycogen and gets little benefit from glycolysis when the supply of oxygen is limited. o Thus anything that interrupts the flow of oxygenated blood to the heart leads quickly to damage — even death — of the affected part. This is what happens in heart attacks. Smooth Muscle Smooth muscle is made of single, spindle-shaped cells. It gets its name because no striations are visible in them. Nonetheless, each smooth muscle cell contains thick (myosin) and thin (actin) filaments that slide against each other to produce contraction of the cell. The thick and thin filaments are anchored near the plasma membrane (with the help of intermediate filaments). Smooth muscle (like cardiac muscle) does not depend on motor neurons to be stimulated. However, motor neurons (of the autonomic system) reach smooth muscle and can stimulate it — or relax it — depending on the neurotransmitter they release (e.g. noradrenaline or nitric oxide, NO). Smooth muscle can also be made to contract  by other substances released in the vicinity (paracrine stimulation) o Example: release of histamine causes contraction of the smooth muscle lining our air passages (triggering an attack of asthma)  by hormones circulating in the blood o Example: oxytocin reaching the uterus stimulates it to contract to begin childbirth. The contraction of smooth muscle tends to be slower than that of striated muscle. It also is often sustained for long periods. This, too, is called tonus but the mechanism is not like that in skeletal muscle. Muscle Diseases The Muscular Dystrophies (MD) Together myosin, actin, tropomyosin, and troponin make up over three-quarters of the protein in muscle fibers. Some two dozen other proteins make up the rest. These serve such functions as attaching and organizing the filaments in the sarcomere and connecting the sarcomeres to the plasma membrane and the extracellular matrix. Mutations in the genes encoding these proteins may produce defective proteins and resulting defects in the muscles. Among the most common of the muscular dystrophies are those caused by mutations in the gene for dystrophin. The gene for dystrophin is huge, containing 79 exons spread out over 2.3 million base pairs of DNA. Thus this single gene represents about 0.1% of the entire human genome (3 x 109 bp) and is almost half the size of the entire genome of E. coli!  Duchenne muscular dystrophy (DMD) Deletions or nonsense mutations that cause a frameshift usually introduce premature termination codons (PTCs) in the resulting mRNA. Thus at best only a fragment of dystrophin is synthesized and DMD, a very severe form of the disease, results.  Becker muscular dystrophy (BMD).  If the deletion simply removes certain exons but preserves the correct reading frame, a slightly-shortened protein results that produces BMD, a milder form of the disease. The gene for dystrophin is on the X chromosome, so these two diseases strike males in a typical X-linked pattern of inheritance. Myasthenia Gravis Myasthenia gravis is an autoimmune disorder affecting the neuromuscular junction. Patients have smaller end plate potentials (EPPs) than normal. With repeated stimulation, the EPPs become too small to trigger further action potentials and the fiber ceases to contract. Administration of an inhibitor of acetylcholinesterase temporarily can restore contractility by allowing more ACh to remain at the site. Patients with myasthenia gravis have only 20% or so of the number of ACh receptors found in normal neuromuscular junctions. This loss appears to be caused by antibodies directed against the receptors. Some evidence:  A disease resembling myasthenia gravis can be induced in experimental animals by immunizing them with purified ACh receptors.  Anti-ACh receptor antibodies are found in the serum of human patients.  Experimental animals injected with serum from human patients develop the signs of myasthenia gravis.  Newborns of mothers with myasthenia gravis often show mild signs of the disease for a short time after their birth. This is the result of the transfer of the mother's antibodies across the placenta during gestation. The reason some people develop autoimmune antibodies against the ACh receptor is unknown. The Cardiac Myopathies Cardiac muscle, like skeletal muscle, contains many proteins in addition to actin and myosin. Mutations in the genes for these may cause the wall of the heart to become weakened and, in due course, enlarged. Among the genes that have been implicated in these diseases are those encoding:  actin  two types of myosin  troponin  tropomyosin  myosin-binding protein C (which links myosin to titin) The severity of the disease varies with the particular mutation causing it (over 100 have been identified so far). Some mutations are sufficiently dangerous that they can lead to sudden catastrophic heart failure in seemingly healthy and active young adults. Reference: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Muscles.html THE RESPIRATORY SYSTEM The Respiratory System and Gas Exchange Cellular respiration involves the breakdown of organic molecules to produce ATP. A sufficient supply of oxygen is required for the aerobic respiratory machinery of Kreb's Cycle and the Electron Transport System to efficiently convert stored organic energy into energy trapped in ATP. Carbon dioxide is also generated by cellular metabolism and must be removed from the cell. There must be an exchange of gases: carbon dioxide leaving the cell, oxygen entering. Animals have organ systems involved in facilitating this exchange as well as the transport of gases to and from exchange areas. Bodies and Respiration Single-celled organisms exchange gases directly across their cell membrane. However, the slow diffusion rate of oxygen relative to carbon dioxide limits the size of single- celled organisms. Simple animals that lack specialized exchange surfaces have flattened, tubular, or thin shaped body plans, which are the most efficient for gas exchange. However, these simple animals are rather small in size. Respiratory Surfaces Large animals cannot maintain gas exchange by diffusion across their outer surface. They developed a variety of respiratory surfaces that all increase the surface area for exchange, thus allowing for larger bodies. A respiratory surface is covered with thin, moist epithelial cells that allow oxygen and carbon dioxide to exchange. Those gases can only cross cell membranes when they are dissolved in water or an aqueous solution, thus respiratory surfaces must be moist. Methods of Respiration Sponges and jellyfish lack specialized organs for gas exchange and take in gases directly from the surrounding water. Flatworms and annelids use their outer surfaces as gas exchange surfaces. Arthropods, annelids, and fish use gills; terrestrial vertebrates utilize internal lungs. Gas exchange systems in several animals. Images from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. The Body Surface Flatworms and annelids use their outer surfaces as gas exchange surfaces. Earthworms have a series of thin-walled blood vessels known as capillaries. Gas exchange occurs at capillaries located throughout the body as well as those in the respiratory surface. Amphibians use their skin as a respiratory surface. Frogs eliminate carbon dioxide 2.5 times as fast through their skin as they do through their lungs. Eels (a fish) obtain 60% of their oxygen through their skin. Humans exchange only 1% of their carbon dioxide through their skin. Constraints of water loss dictate that terrestrial animals must develop more efficient lungs. Gills Gills greatly increase the surface area for gas exchange. They occur in a variety of animal groups including arthropods (including some terrestrial crustaceans), annelids, fish, and amphibians. Gills typically are convoluted outgrowths containing blood vessels covered by a thin epithelial layer. Typically gills are organized into a series of plates and may be internal (as in crabs and fish) or external to the body (as in some amphibians). Gills are very efficient at removing oxygen from water: there is only 1/20 the amount of oxygen present in water as in the same volume of air. Water flows over gills in one direction while blood flows in the opposite direction through gill capillaries. This countercurrent flow maximizes oxygen transfer. Countercurrent flow in a fish. Images from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. Tracheal Systems Many terrestrial animals have their respiratory surfaces inside the body and connected to the outside by a series of tubes.Tracheae are these tubes that carry air directly to cells for gas exchange. Spiracles are openings at the body surface that lead to tracheae that branch into smaller tubes known as tracheoles. Body movements or contractions speed up the rate of diffusion of gases from tracheae into body cells. However, tracheae will not function well in animals whose body is longer than 5 cm. Respiratory system in an insect. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. Lungs Lungs are ingrowths of the body wall and connect to the outside by as series of tubes and small openings. Lung breathing probably evolved about 400 million years ago. Lungs are not entirely the sole property of vertebrates, some terrestrial snails have a gas exchange structures similar to those in frogs. Lungs in a bird (top) and amphibian (bottom). Images from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. Respiratory System Principles 1. Movement of an oxygen-containing medium so it contacts a moist membrane overlying blood vessels. 2. Diffusion of oxygen from the medium into the blood. 3. Transport of oxygen to the tissues and cells of the body. 4. Diffusion of oxygen from the blood into cells. 5. Carbon dioxide follows a reverse path. Functional unit of a mammalian lung. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. The Human Respiratory System This system includes the lungs, pathways connecting them to the outside environment, and structures in the chest involved with moving air in and out of the lungs. The human respiratory system. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. Air enters the body through the nose, is warmed, filtered, and passed through the nasal cavity. Air passes the pharynx (which has the epiglottis that prevents food from entering the trachea).The upper part of the trachea contains the larynx. The vocal cords are two bands of tissue that extend across the opening of the larynx. After passing the larynx, the air moves into the bronchi that carry air in and out of the lungs. The lungs and alveoli and their relationship to the diaphragm and capillaries. Images from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. Bronchi are reinforced to prevent their collapse and are lined with ciliated epithelium and mucus-producing cells. Bronchi branch into smaller and smaller tubes known as bronchioles. Bronchioles terminate in grape-like sac clusters known as alveoli. Alveoli are surrounded by a network of thin-walled capillaries. Only about 0.2 µm separate the alveoli from the capillaries due to the extremely thin walls of both structures. Gas exchange across capillary and alveolus walls. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. The lungs are large, lobed, paired organs in the chest (also known as the thoracic cavity). Thin sheets of epithelium (pleura) separate the inside of the chest cavity from the outer surface of the lungs. The bottom of the thoracic cavity is formed by the diaphragm. Ventilation is the mechanics of breathing in and out. When you inhale, muscles in the chest wall contract, lifting the ribs and pulling them, outward. The diaphragm at this time moves downward enlarging the chest cavity. Reduced air pressure in the lungs causes air to enter the lungs. Exhaling reverses theses steps. Inhalation and exhalation. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. Diseases of the Respiratory System The condition of the airways and the pressure difference between the lungs and atmosphere are important factors in the flow of air in and out of lungs. Many diseases affect the condition of the airways.  Asthma narrows the airways by causing an allergy-induced spasms of surrounding muscles or by clogging the airways with mucus.  Bronchitis is an inflammatory response that reduces airflow and is caused by long-term exposure to irritants such as cigarette smoke, air pollutants, or allergens.  Cystic fibrosis is a genetic defect that causes excessive mucus production that clogs the airways. The Alveoli and Gas Exchange Diffusion is the movement of materials from a higher to a lower concentration. The differences between oxygen and carbon dioxide concentrations are measured by partial pressures. The greater the difference in partial pressure the greater the rate of diffusion. Respiratory pigments increase the oxygen-carrying capacity of the blood. Humans have the red-colored pigment hemoglobin as their respiratory pigment. Hemoglobin increases the oxygen-carrying capacity of the blood between 65 and 70 times. Each red blood cell has about 250 million hemoglobin molecules, and each milliliter of blood contains 1.25 X 1015 hemoglobin molecules. Oxygen concentration in cells is low (when leaving the lungs blood is 97% saturated with oxygen), so oxygen diffuses from the blood to the cells when it reaches the capillaries. Effectiveness of various oxygen carrying molecules. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. Carbon dioxide concentration in metabolically active cells is much greater than in capillaries, so carbon dioxide diffuses from the cells into the capillaries. Water in the blood combines with carbon dioxide to form bicarbonate. This removes the carbon dioxide from the blood so diffusion of even more carbon dioxide from the cells into the capillaries continues yet still manages to "package" the carbon dioxide for eventual passage out of the body. Details of gas exchange. Images from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission. In the alveoli capillaries, bicarbonate combines with a hydrogen ion (proton) to form carbonic acid, which breaks down into carbon dioxide and water. The carbon dioxide then diffuses into the alveoli and out of the body with the next exhalation. Control of Respiration Muscular contraction and relaxation controls the rate of expansion and constriction of the lungs. These muscles are stimulated by nerves that carry messages from the part of the brain that controls breathing, the medulla. Two systems control breathing: an automatic response and a voluntary response. Both are involved in holding your breath. Although the automatic breathing regulation system allows you to breathe while you sleep, it sometimes malfunctions. Apnea involves stoppage of breathing for as long as 10 seconds, in some individuals as often as 300 times per night. This failure to respond to elevated blood levels of carbon dioxide may result from viral infections of the brain, tumors, or it may develop spontaneously. A malfunction of the breathing centers in newborns may result in SIDS (sudden infant death syndrome). As altitude increases, atmospheric pressure decreases. Above 10,000 feet decreased oxygen pressures causes loading of oxygen into hemoglobin to drop off, leading to lowered oxygen levels in the blood. The result can be mountain sickness (nausea and loss of appetite). Mountain sickness does not result from oxygen starvation but rather from the loss of carbon dioxide due to increased breathing in order to obtain more oxygen. http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookRESPSYS.html