Muscle Contraction and Fatigue PDF

CLOUD MODULE CONTENT NOTES MODULE ONE: MUSCLE CONTRACTION AND FATIGUE SKELETAL MUSCLE We have more than 600 muscles in the body and they determine our ability to do things Muscles provide heat to maintain body temperature It stores the majority of glucose and amino acids that we consume Muscle is hi...

CLOUD MODULE CONTENT NOTES MODULE ONE: MUSCLE CONTRACTION AND FATIGUE SKELETAL MUSCLE We have more than 600 muscles in the body and they determine our ability to do things Muscles provide heat to maintain body temperature It stores the majority of glucose and amino acids that we consume Muscle is highly adaptable and will adapt to the stress placed upon it Muscle is able to grow to produce more force and adapt to increase oxygen capacity to reduce fatigue Muscles are bound in bundles, referred to as a fascicle and are covered by an endomysium layer (connective tissue) The contractile proteins in myofibrils are responsible for force generation. The neuromuscular junction (NMJ) and motor units are all crucial in muscle contraction. The interaction of the contractile proteins, actin and myosin, produces force within skeletal muscle. Actin and myosin filaments are arranged in a highly structured unit called sarcomeres Other important organelles in skeletal muscle include the sarcoplasmic reticulum and the transverse tubules, which together form the triad. A motor unit includes a peripheral motor neuron (nerve) and all of the muscle fibres that it innervates The smallest functional force producing unit within skeletal muscle is the sarcomere. It is intracellular, which makes sense, and it is the collection of sarcomeres that makes up the large myofibrils, which organise the sarcomeres within cells. While collections of cells (fibres) form the fascicles, with collections of fascicles making up the whole muscle. The contractile proteins within sarcomeres are arranged in such a way that they overlap to produce a light and dark banded pattern in an extremely ordered way when viewed under a microscope, and therefore the arrangement of sarcomeres is clearly visible. A motor unit within skeletal muscle is a somatic alpha-motor neuron and all of the muscle fibres that it innervates. It is important to understand the structural relationship between a neuron and ALL the muscle fibres it innervates forming a motor-unit as this is what we use to build muscle force during exercise, i.e. motor-unit recruitment. Only one neuron innervates a skeletal muscle fibre as more than one would generate uncoordinated contraction. The NMJ, it is also sometimes called the synaptic cleft, or the junctional space. It has a few different names. Important to recognise it is a space and that there is no direct connection between the motoneuron and the skeletal muscle fibre. Hence, we need a process to translate the action potential in the neuron to achieve an action potential in the muscle fibre. There are 3 steps of muscle contraction: neuromuscular transmission, excitation contraction coupling and the cross bridge cycle. Performing movement requires a coordination of neural signals generated in the CNS, transmission of signals along peripheral motor nerves, transfer of neural signal into the muscle and contraction of muscle fibres. Our motor cortex is the area of brain that is involved in the control of voluntary movement, this region of the brain makes the signal to do the movement. Motor nerves are what carries the signal from the CNS to the skeletal muscle. These signals are transmitted via action potentials. Excitation is the process of the neural impulse into the muscle to generate movement. They travel down the T Tubules to generate contraction and cause excited fibres Once the fibres for excited, this causes contraction of the actin and myosin filaments, causing a cross bridge 3 STAGES OF FORCE GENERATION 1. Neuromuscular transmission: neural signals are sent from the motor cortex to the NMJ. From there, it must be transferred to the muscle fibre for contraction to occur. This process has 4 steps: - action potentials arrive at the motor neuron terminal. - vesicles containing the neurotransmitter acetyl choline release their contents into the synaptic cleft, acetyl choline binds to receptors on the sarcolemma of the muscle fibre and this allows for an influx of sodium ions into the muscle - movement of sodium into the muscle generates an action potential, AP's are transmitted along the t tubules and deep into the muscle fibre. - action potentials travels into the muscle down T tubules to initiate calcium release from the sarcoplasmic reticulum - synaptic boutons can release neurotransmitters. Under these are junctional folds that have receptors for acetylcholine. 2. Excitation Contraction Coupling: this links step 1 and 3 together. The aim is to use the AP within the T Tubules to prep the muscle for the formation of cross bridges and force generation. This occurs through the release of calcium from the sarcoplasmic reticulum which then binds to the proteins on the actin filaments. Role of: -T Tubulues: invaginations of the sarcolemma that penetrate deep into each muscle fibre. Evident at each Aband-I band junction and therefore approach each myofibril and therefore every sarcomere, they rapidly and evenly distribute action potentials throughout all sarcomeres in the muscle. - Sarcoplasmic Reticulum (calcium storage): this is the membrane network around each myofibril and it has 2 distinct sections: 1. Terminal cisternae: this releases calcium into the cytosol and has sac like structures near the Z line/I band regoin 2. Longitudinal tubules: uptakes calcium from the cytosol and is located around the A band - The Triad: Includes 1 T-tubule and flanked each side by the terminal cisternae of the Sarcoplasmic Reticulum. Structure allows efficient transmission of the action potential from the T-tubule to stimulate Ca2+ release from the Sarcoplasmic Reticulum 3. Cross Bridge Cycling: this is the interaction between actin and myosin. At rest, cross bridges cannot form until calcium concentration rises. Myosin is a thick filament contractile protein and sits centrally in the sarcomere, it also has a "head" and "tail" part to it. The head exhibits ATPase activity, meaning it's enzyme that uses the energy currency in the cell (ATP) and is also a binding site for actin. The tail contains a flexible hinge region, allow for the head to rotate during cross bridge cycling. The tail of each myosin protein bind with other myosin proteins to for the myosin filament. Actin is a smaller/thinner protein and sits in the outer edges of the sarcomere and is connected to the Z line. It contains a binding site for myosin but it's surrounded by regulatory proteins tropomyosin and a protein complex called troponin. At rest cytosolic concentrations of Ca2+ are low and the myosin binding sites on Actin are blocked by the presence of tropomyosin, which sits above these binding sites. However, when the action potential arrives and Ca2+ is released from the SR, this causes cytosolic concentrations to become HIGH. Ca2+ binds to the troponin complex which causes a change in the shape of the complex. This shape change moves tropomyosin to expose the myosin binding site on Actin (see Figure B below). THE CROSS BRIDGE CYCLE STAGES Stage 1: resting state. Myosin is energised, ATP has been split into ADP and Pi, energy is stored in the myosin head and the myosin binding site of actin is blocked by tropomyosin. Stage 2: calcium is released and binds to troponin, myosin binding site of actin is exposed and myosin head binds to actin to form the cross bridge Stage 3: Pi is released from the myosin head and allows for a change in the shape of the myosin molecule Stage 4: energy is released to generate the power stoke. ADP is released from the myosin head, actin and myosin filaments slide pass each other. Stage 5: the myosin head binds to a new ATP molecule and allows the detachment of the actin myosin filaments. Stage 6: ATP is hydrolysed and phosphate binds to myosin, causing cross bridge to return to it's original position. Neuromuscular transmission enables to transfer of the electrical signal in the neuron into the muscle fibre The T-tubules allow the action potential to be transmitted deep into the muscle fibre to reach all of the sarcomeres Calcium ions (CA2+) are released from the sarcoplasmic reticulum and are essential to enable the formation of cross-bridges A cross-bridge is formed between actin and myosin, and a conformational change in the shape of the myosin head allows the actin and myosin filaments to slide passed each other which shortens the sarcomere When all the sarcomeres across the length of the muscle shorten simultaneously, the whole muscle contracts to generate force. Acteylcholine (Ach) is a common neurotransmitter and it is the only neurotransmitter used for neuromuscular transmission within skeletal muscle. The SR is fundamental to muscle by providing a ready store of Ca2+, a mechanism to release Ca2+ to initiate the contractile mechanism when the muscle fibre is activated, and a mechanism to remove and re-store Ca2+ that drives relaxation of muscle after a contraction. The triad is a specialised junction of the sarcoplasmic reticulum (SR) and transverse tubules (T-tubules) located either side of the Z-lines of the sarcomere. It specialises in transducing the electrical action potential in the T-tubule into a physical release of calcium ions (Ca2+) from the sarcoplasmic reticulum (SR). At the conclusion of the power stroke in the cross-bridge cycle, the myosin head has lost the by-products of ATP hydrolysis (ATP and Pi) and is now available to bind another ATP, which then causes the detachment of actin and myosin. What drives the eventual relaxation of skeletal muscle when there is no longer an activating stimulus coming from the associated alpha motoneuron? Actively pumping calcium ions (Ca2+) from the cytosol into the sarcoplasmic reticulum (SR), this is one of the most rapid processes within skeletal muscle and calcium ions are essential to allow continued contraction. Quickly removing these causes relaxation, and it is achieved by an active reuptake process embedded within the sarcoplasmic reticulum membrane. MUSCLE FIBRE TYPES We have 2 main categories for muscle fibre types, Type 1 and Type 2 Type 2 is further divided into type 2a and type 2x Most muscles within the body have a combo of the 3 types, they can all be influenced by genetics and exercise training. Type 1 and type 2x fibres sit at opposite ends of the spectrum, but type 2a fibres sit somewhere in the middle. Fast twitch fibres appear white in colour and slow twitch fibres appear red in colour. The colour of these fibres is due to the concentration of myoglobin and its blood supply. The reason for the slow twitch being more red is that it has more myoglobin and a higher density of capillaries. Our postural muscles are typically slow twitch due to them being 'on' all the time. Major muscle groups tend to be a combo of both slow and fast twitch fibres. The type of myosin heavy chain is a robust method to classify fibre types as it relies upon a large heavy structural protein that is difficult to change. Hence, it is reasonably stable in any muscle fibre, yet it can change over time with chronic (long-term) exercise training. Type 1 fibres have a higher mitochondrial content Slow Twitch Fast twitch (Type 2a Fast Twitch (Type 2x) Muscle Fibre Diameter Small intermediate large Mitochondrial density High Intermediate low Structural Aspects Capillary density High Intermediate low Myoglobin content High Intermediate low SR density Low High high Actin and Myosin content Low High high Contraction Time Slow Fast fast Relaxation time Slow Fast fast Force production Low Intermediate high Fatiguability Low Intermediate high Phosphocreatine stores (PCr) Low Intermediate high Glycogen stores Low Intermediate high Intramuscular triglyceride (IMTG) stores High Intermediate low Myosin ATPase activity Low High high Glycolytic enzyme activity Low High high Oxidative enzyme activity High Intermediate Low Functional Aspects Metabolic Aspects MUSCLE FIBRE FORCE REGULATION The force a single muscle fibre produces is determined by the stimulation frequency and the length of the muscle fibre The size principle of muscle fibre recruitment explains how the force requirements of a particular task are met. The order of motor unit recruitment, and therefore muscle fibre recruitment, is determined by the size of the motor unit with small, slow motor units recruited at low force requirements. Muscle size and neural factors combine to determine muscle strength Cross sectional area is directly related to how many sarcomeres within the muscle are arrange in parallel, which is an arrangement that produces much more force than sarcomeres arranged in series. The faster nature of type-II fibres means they require higher frequencies of stimulation to produce a maximal tetanic contraction To increase force output, more motor units need to be recruited. Given the setup of skeletal muscle fibres within motor units being activated by a single alpha motoneuron, it is these discrete units that are “recruited” to increase force output during exercise. MUSCLE FIBRE TRAINABILITY AND RELATION TO PERFORMANCE Muscle fibre type is highly varied across the population. In athletes, fibre type is generally suited to the sporting event but it is only one of a number of factors determining sporting success Improvements in strength with resistance training are due to neural factors and muscle fibre hypertrophy Endurance training improves the oxidative capacity of the muscle through increases in the ability to transport and use O2. Muscle fibre type shifts can occur with prolonged training but these take a long time and there is a limited ability to transform muscle fibre type. Muscle fibre adaptations to training can occur independently of shifts in fibre type (i.e. fibre hypertrophy or increased oxidative capacity can occur across all fibres). Longitudinal studies have shown that strength training results in a change in type 2a muscle fibres. While the expectation is to converge toward a faster type-II profile it is in fact the Type-IIa fibres that proliferate given they carry slightly greater metabolic fatigue resistance that is needed for resistance exercise given all of the aerobic recovery between repeated sets or sprints of the training Increased capillary density contributes to early adaptations to increases in oxidative capacity in type 1 fibres when exposed to endurance training. The growth of new blood vessels (termed angiogenesis) in the form of capillaries is an early adaptation to endurance training and occurs within 1-2 weeks of endurance training. This adaptation reduces the diffusion distance of oxygen from the circulation to the mitochondria and enables improved oxygen delivery and utilisation by the working muscle. MUSCLE FATIGUE Can either be central or peripheral T-tubules are responsible for delivering action potentials to the muscle to stimulate contraction. If this is altered, contraction can be less or fail entirely. This can be affected by the amount o f K+ within the cell K+ Na+ Control Fatigue Intracellular 175 130 Extracellular 5 10 Intracellular 5 8 Extracellular 143 143 There is little consensus about the causes of fatigue which likely involves multiple mechanisms Short intense exercise is due to peripheral (i.e. muscle) factors whereas exercise >10 s involves both peripheral and central factors Fatigue related to intense exercise occurs at multiple sites and involves the accumulation of by-products of ATP breakdown Muscle glycogen depletion appears to be the primary mechanism for fatigue in prolonged moderate to high intensity exercise In exercise lasting less than 10 seconds the peripheral system would be larger component of fatigue. The mechanisms of fatigue relating to short, all-out exercise appear unrelated to central mechanisms and are instead peripheral in nature. Mechanisms of fatigue appear to be related to a combination of neural, mechanical and/or energetic events in skeletal muscle. On the other hand, central fatigue is generally only seen in prolonged exercise with a reduction in ‘arousal’ and a reduction in the ability to voluntarily contract the muscle to maximum levels. A failure to recruit motor units is central fatigue. Central fatigue is more commonly observed in exercise lasting >10 seconds and refers to a failure in the ability to voluntarily ‘activate’ motor units. This is observed when electrically stimulating the muscle can increase force production beyond a maximal voluntary contraction, which demonstrates the fatigue originates in the central nervous system rather than the muscle itself. A failure to recruit motor units demonstrates that the fatigue occurs above the level of the neuromuscular junction and skeletal muscle and is related to changes in the central nervous system and reductions in ‘arousal’ rather than changes in peripheral neurones. During high frequency stimulation of muscle to fatigue, there is a decrease of intracellular potassium ions with the muscle fibre. During fatiguing contractions the sodium-potassium (Na+/K+) pump is unable to pump potassium into the muscle at a sufficient rate, resulting in potassium accumulation outside the cell. This results in depolarisation and a reduction in amplitude of the action potential. Also, during fatigue there would be a failure to pump potassium back into the cell, so there would more likely be an increase in extracellular potassium. Hydrogen ions are related to the generation of lactate and a decline in pH, therefore hydrogen ion concentrations are likely to increase during heavy exercise. While disturbances in calcium dynamics have been implicated in fatigue, this is related to the release and reuptake of calcium from the sarcoplasmic reticulum. Calcium is not lost from the muscle during fatiguing contractions. With the onset of peripheral fatigue, there are more cross-bridges attached in a weak (as opposed to strong) binding state. The molecule that most likely inhibits attached cross bridges moving from a weak binding state to a strong binding state is Inorganic Phosphate (Pi). When ATP demand outstrips the ability of the muscle to resynthesize ATP there is an accumulation of ATP breakdown products, one of which is inorganic phosphate (Pi). Loss of calcium dynamics (i.e. release and reuptake by the sarcoplasmic reticulum) may be involved in peripheral fatigue. However, the mechanism is related to the role of calcium binding to troponin, and facilitating cross-bridge formation, rather than the conversion of bound actin and myosin into the strong binding state. ATP concentrations in the muscle rarely decline significantly and ATP binding is required for the release of the actin-myosin cross-bridges NOT the conversion into the strong binding state. ADP is released from the myosin head during the power stroke phase of the cross-bridge cycle. ADP may increase during fatigue but is more likely to play a role in contraction velocity due to its inhibitory role on myosin ATPase. A decline in calcium reuptake results in longer relaxation time. Calcium reuptake into the sarcoplasmic reticulum is a requirement for the muscle to enter the relaxation phase of the contraction cycle. It is possible that a slowing of the SR calcium pump causes a slowing of relaxation time during peripheral fatigue. On the other hand, reduced ability of muscle membrane to conduct an action potential is dependent on the concentrations on potassium and sodium across the sarcolemma. A loss of potassium from the muscle results in a failure to conduct the action potential and is unrelate to calcium uptake. Contraction velocity is determined by the rate of cross-bridge cycling which is reliant on the activity of myosin ATPase. This is unaffected by changes in calcium reuptake. The decline in peak tension is due either a reduction in the number of cross bridges per muscle cross-sectional area or force produced per cross bridge. These are mostly affected by the release of calcium, calcium-troponin binding and the cross bridges in the strong binding state. Skeletal muscle fatigue during prolonged exercise is likely the result of muscle glycogen depletion. There is a strong correlation between muscle glycogen content and time to fatigue during prolonged (>1 h) submaximal exercise. Muscle glycogen depletion is likely associated with an energy crisis where ATP supply cannot meet ATP demand. A decline in muscle pH is unlikely to occur durig prolonged exercise of a submaximal intensity. There is little reliance on the phosphagen system for ATP resynthesis during prolonged submaximal exercise, therefore creatine phosphate levels and inorganic phosphate levels are unlikely to be important in fatigue of this nature. MODULE TWO: METABOLISM METABOLISM OVERVIEW Muscles are poor at storing ATP There is only enough ATP stored in the muscle for 1 second The body has 3 energy systems: phosphagen system, anaerobic glycolysis and aerobic metabolism Metabolism refers to a collective of chemical responses in the cells that both breakdown and synthesize molecules During exercise, energy expenditure can increase 25x that of our resting rate due to the ATP needed for muscle contraction. Most of the ATP stores are needed for cross bridge cycling, some of release and uptake of calcium and the maintenance of potassium and sodium levels. How each energy system contributes to determined by the intensity of the exercise. ATP: the energy currency within the muscle. Is made up of an adenosine head and 3 phosphate molecules. Used to make energy for muscle contraction. ATPase is an enzyme to break down ATP and takes off one of the phosphate molecules to make energy for muscle contraction. Following this, we're left with ADP Resting concentrations of ATP aren't really changed during exercise, 5 mmol.l ATP is constantly being remade to sustain muscle contraction and concentrations in the cell. If we have energy available from the breakdown of fuels, that leftover molecule binds back to the ADP to then make ATP We have catabolic and anabolic reactions. Catabolic: breakdown larger molecules into smaller molecules. This typically refers to the 3 macros we eat. The larger the molecule, the more energy. This breakdown releases energy. ATP is also used to make small molecules into large ones and stimulate anabolic reactions. This requires energy. Typically anabolic reaction is protein synthesis. Supply and demand perspective. When we exercise, ATP demand increases for muscle contraction. ATP resynthesis demand increases from ADP + Pi. The intensity of the exercise will determine the demand of ATP and the breakdown of fuel stores. There are 3 different processes that demand ATP, the cross bridge cycling process requires the most ATP, roughly 70%, calcium cycling is roughly 25% and ionic cycling is about 5%, that maintains sodium and potassium homeostasis. When we exercise, this increases. ATP resynthesis is supplied via glycolysis, high energy phosphate transfer and oxidative phosphorylation The phosphagen system produces the highest production of ATP, then glycolysis, then CHO and lastly fat. Prolonged endurance exercise, the ATP requirement is a bit lower, so we will use the aerobic energy system, meaning we tend to use carbs and fats for this. Sprinting activity then relies on the phosphagen system, as it we resynthesis ATP a lot faster. Lactate is the result of pryuvate End of module questions: 1. Which ATP dependent process within the muscle largely explains the increase in energy consumption during dynamic exercise? Cross bridge cycling. ATP is required to bind to mysosin heads to allow detachment of the actin-myosin crossbridges. This is an important step in the cross-bridge cycle, the subsequent splitting of ATP by the enyzme myosin ATPase is required for the attachment of the myosin head to the actin binding site. This process accounts for ~70% of the ATP demand during exercise. Calcium reuptake into the sarcoplasmic reticulum is increased during muscle contraction to permit contraction and relaxation cycles during dynamic exercise. This process is dependent on ATP and requires the activity of Ca2+ ATPase. However, it acounts for ~25% of the increase in ATP demand during exercise. ATP is required to maintain the resting membrane potential of the muscle fibre by pumping sodium (Na+) out of the cell, and pumping potassium (K+) into the cell. The action of Na+/K+ pump is dependent on ATP breakdown by the Na+/K+-ATPase. The activity of the pump increases during exercise in order to regain the resting membrane potential following contraction but this accounts for ~5% of total ATP demand during exercise. Glucose transport into the muscle cell increases with muscle contraction and is an important event to maintain glucose availability to fuel glycolysis (I.e. anaerobic production of ATP from glucose). However, glucose transport occurs passively through the glucose transporter (GLUT4) and is not dependent on ATP. 2. During intense exercise lasting less than 10 seconds, which enzyme is mostly responsible for the resynthesise of ATP? Creatine kinase. Creatine kinase catalyses the reaction to liberate a phosphate group from phosphocreatine, which enables the resynthesis of ATP from ADP. The phosphocreatine system is the dominant energy source during intense exercise. However the PCr stores are limited and can only provide sufficient rates of ATP resynthesis for ~5-7 seconds of exercise. Adenylate cyclase is involved in the resynthesis of ATP by providing a phosphate group from ADP. However, it is only involved in ATP resynthesis during very intense exercise and is minor importance when compared to phosphocreatine. Myosin ATPase catalyses the splitting of ATP to form ADP and Pi. The activity of myosin ATPase does increase during exercise but the reaction breaks down ATP, it is not involved in ATP resynthesis. Lactate dehydrogenase generates lactate from the pyruvate that is generated by the reactions of glycolysis. Although lactate dehydrogenase activity and therefore lactate production increases during intense exercise to allow the reactions of glycolysis to continue, it becomes more important in exercise lasting 10-30 seconds. 3. Which metabolic process involves the sequential breakdown of glucose to form pyruvate? Glycolysis Glycolysis involves the breakdown of glucose to form pyruvate, which can then either be further broken down to acetyl CoA or converted to lactate. The rate limiting enzyme involved in glycolysis is phosphofructokinase. While glycogenolysis does generate pyruvate, glycogen is the starting substrate in the reaction. Once a glucose molecule is broken from glycogen, it follows the standard reactions of glycolysis. Acetyl CoA enters the citric acid cycle (Krebs cycle) and is broken down through a sequential series of reactions. Glucose transport into the muscle cell increases with muscle contraction and is an important event to maintain glucose availability to fuel glycolysis (I.e. anaerobic production of ATP from glucose). However, glucose transport occurs passively through the glucose transporter (GLUT4) and is not dependent on ATP. 4. The main role of the citric acid cycle is to generate H+ from the breakdown of citrate, which are accepted by the H+ carriers and NAD and FAD. Where in the cell does the citric acid cycle take place Mitochondrial matrix 5. Which metabolic process involves the sequential breakdown of citrate and results in the release of several hydrogen ions (H+) which are accepted by the carriers NAD and FAD. The citric acid cycle The TCA cycle (or Krebs cycle) takes place in the matrix of the mitochondria and involves the sequential breakdown of citrate. Through this process H+ are released which are carried by NAD and FAD to the electron transport chain. In summary, this process results in the generation of 3 x NADH, 1 x FADH, 1 x CO2 and 1 x ATP. Oxidative phosphorylation describes the process of ATP generation through electrons passing along carriers of the inner mitochondrial membrane. This is the end reaction of aerobic metabolism and requires oxygen. β-oxidation involves the breakdown of fatty acids to generate numerous molecules of acetyl CoA. The acetyl CoA that is generated can then enter the citric acid cycle. Lipolysis is the breakdown of the stored form of fat (triacylglycerol) into its component parts, 3 x fatty acids and 1 x glycerol. SPRINT EXERCISE Anaerobic Metabolism Any exercise that is less than 30 seconds has ATP generated via the anaerobic systems They do also contribute in some way to endurance events Phosphagen and glycolysis are the anaerobic metabolisms 0.3L per minute is resting VO2 just to keep us alive, once exercise is factored in, this goes up Takes about 2-3 minutes for the body to match the VO2 requirements for exercise via aerobic metabolism. There is a shortfall in ATP production and therefore the body has to tap into the anaerobic metabolism VO2 max can plateau when an individual meets their threshold High intensity exercise relies heavily on anaerobic ATP production. When there is an O2 deficit, the anaerobic metabolism with make up for the aerobic metabolism. This can occur at the onset of exercise, increasing exercise intensity and during sprint exercise The size of the O2 deficit will determine the EPOC uptake ATP rarely, very rarely, is only ever supplied from one energy system, especially during high intensity exercise There is a heavy dependence on the phosphagen system during 30 second exercise bouts The breakdown of PCr results in a an uptake in free creatine within the body PCr depletes at a high rate during high intensity exercise, however remains relatively stable during moderate intensity exercise For PCr to be replenished following sprint exercise, a phosphate must be donated from ATP. This occurs through the aerobic system and this also contributes to the EPOC effect 20 seconds rest is not enough time for PCr to be replenished, but 40 seconds is enough to get them back to 80% For glycolysis, most pyruvate will be made into lactate due to the high intensity Benefits of sprint training Greater ATP turnover in both the PCr and glycolysis systems Better pH maintenance and buffering of H+ ions Delayed fatigue onset Better ATP turnover in the aerobic system, higher mitochondrial and capillary density Muscle hypertrophy Conversion to type 2a muscle fibres Increases in max muscle power Anaerobic glycolysis is the dominant energy system for ATP resynthesis in an all out sprint Endurance Exercise Carbs are stored of muscle glycogen within the muscle or as glucose, which circulates in the bloodstream Fats are stored as intramuscular triglycerides or as fatty acids, also circulating the bloodstream Glucose can also be stored in the liver and fats can be stored in adipose tissue Carb Stores Liver: 60g/240 kcal Blood: 10g/40 kcal Muscle: 350g/1400 kcal Fat Stores Muscle: 500g/3850 kcal Adipose tissue: 14kg/100,000 kcal We increase our body's ability to utilise fatty acids for energy with endurance training Hormonal Regulation of Fuel Supply Blood needs to contain enough glucose to fuel the muscles and to maintain normal levels Low glucose can be fatal cause the brain needs it to survive. Fatty acids also need to be available during low-moderate intensity exercise. Blood glucose can be taken up by all tissues in the body and it can be stored as glycogen in the liver and muscle. It can be converted to adipose tissue if there is too much excessive. The brain takes up most of the glucose in the body. The liver can also breakdown stored glycogen into glucose so that it can be released into the circulation. In a fasted state, most of the glucose is taken up by the brain. In a fed state, glucose is higher and the liver stops producing it. During exercise, glucose uptake rises due to the muscles needing glucose. The liver can also kick back on here due to the higher demands of glucose. These concentrations are tightly regulated in the body. There needs to be enough glucose for essential bodily functions and also for the generation of ATP during exercise. Our nervous system and endocrine system work together to regulate homeostasis. Aka the Neuro-endocrine response. Hormones exert their action via membrane transport and activation of second messengers End of module questions 1. Which hormonal responses stimulate the mobilization of free fatty acids from adipose tissue and increased glucose output from the liver? Insulin promotes glucose and fatty acid storage by stimulating glucose transport and storage, and promoting fatty acid storage in triacylglycerol. Therefore, a decrease in insulin concentration during exercise would aid fuel mobilisation. Glucagon promotes mobilisation of fatty acids from adipose tissue and glucose from the liver. Therefore an increase in glucagon with exercise would also aid in supporting fuel availability. On the other hand, an increase in insulin concentration during exercise would aid fuel storage rather than mobilisation. A decrease in glucagon with exercise would supporting fuel storage rather than mobilisation. 2. Which process directly contributes to the increase in liver glucose output during exercise The liver stores glycogen which can be broken down through the action of glycogen synthase, which is primarily stimulated by the increase in catecholamines with high intensity exercise. Gluconeogenesis can also contribute to the increase in liver glucose output by synthesizing glucose from non-carbohydrate sources. On the other hand, through lipolysis, the breakdown of triacylglycerol will increase the release of fatty acids from adipose tissue. This may assist in preserving blood glucose concentrations indirectly through the increase in fatty acid oxidation while reducing carbohydrate oxidation. Beta-oxidation refers to the breakdown of fatty acids into acetyl CoA and is a necessary step in ATP production from fatty acids. Glucose uptake into skeletal muscle will increase during high intensity exercise, however glucose uptake will be lower in other tissues due to the action of adrenaline and lower insulin concentrations. However, this step is unrelated to glucose production from the liver. Glycogen is a banded structure of multiple glucose units Muscle Glycogen can be found in Subsarcollemal (SS) Glycogen - Located just underneath the cell membrane, hence terms subsarcollemal glycogen. Intermyofibrillar (IMF) Glycogen – located in between the myofibrils and in close proximity to the triad (sarcoplasmic reticulum and T-tubules). Intramyofibrillar (Intra) Glycogen – located within the myofibrils and very close to the contractile proteins, actin and myosin. Muscle glycogen is regulated by the enzyme phosphorylase, which is activated by the circulating factors that occur as a result of exercise, eg: build up of calcium catecholamines, etc. Catecholamines are secreted from the adrenal gland through stimulation by the sympathetic nervous system. The catecholamine response to exercise is highly dependent on exercise intensity, with the highest concentrations reached during high intensity exercise (refer back to module 2.4.3). The muscle factors (Ca2+, Pi and AMP) will accumulate in the muscle during exercise. Calcium is required to stimulate muscle contraction (Module 1.2.3) and Pi and AMP are products of ATP breakdown (Module 1.2.5). Therefore, the accumulation of these factors will also be related to exercise intensity – with greater concentrations observed during higher intensity exercise. GLUT4 is a glucose transporter that accumulates within the cell membrane after exercise. Liver Glucose Production There is an increase in skeletal muscle glucose uptake during exercise The liver is important for whole body metabolism The liver is the only thing that supplies glucose to blood glucose levels Hepatic glucose production is liver glucose production Glucose production from the liver tends to increase as exercise increases over time. For some exercise conditions, hepatic glucose production begins to fall, this is due to liver glycogen levels becoming critical and cannot continue. It can directly breakdown glucose in the liver (glycogenolysis) and transport it into the circulation The second way it can make glucose, is by converting non carb based sources into glucose and release it back into the circulation. Majority of glucose made by the liver is from glycogen. There are small contributions from lactate, amino acids and glycerol. At rest, there is a 25% contribution from amino acids and lactate to glucose production The sympathetic NS directly stimulates production Catecholamines, cortisol, growth hormone and glucagon contribute to production also. Insulin supressed glucose production from the liver during carbohydrate feeding. If exercise were performed to exhausted, than 70% of VO2 max would see the greatest muscle glycogen depletion. This exercise intensity is high enough for muscle glycogen to be the dominant fuel, yet this intensity can be sustained for ~90 minutes, which is long enough to see substantial muscle glycogen depletion. The rate of muscle glycogen depletion would be highest at 100%, however, as this intensity of exercise can only be sustained for a few minutes, the total reduction in muscle glycogen would be low. Although exercise of intensity at 50% can be sustained for a prolonged period of time, the rate of muscle glycogen depletion would be modest, as fatty acids from both muscle TAG and plasma would be the dominant fuel sources. Although exercise of intensity at 30% can be sustained for a many hours, the rate of muscle glycogen depletion would be low. At this exercise intensity, plasma fatty acids would be the dominant fuel sources. The movement of GLUT4 to the plasma membrane is the primary mechanism that transports glucose to skeletal muscle. In response to muscle contraction, the glucose transporter GLUT4 moves from the cytosol to the periphery of the cell where it becomes incorporated in the cell membrane. Glucose can then pass through this transporter via diffusion. On the other hand, a rise in insulin concentration after a meal does stimulate glucose uptake into skeletal muscle via the glucose transporter GLUT4. However, insulin concentrations decrease during exercise so that glucose is not taken up by other tissues (I.e. tissues other than the working muscle) where glucose requirements are low. Phosphofructokinase is the rate limiting enzyme in glycolysis and is not directly involved in glucose transport. However, a high rate of glycolysis can assist in glucose transport as it will maintain low levels of glucose within the cell which will assist in maintaining a diffusion gradient between the blood (high glucose) and the muscle (low glucose). GLUT1 is a glucose transporter but it plays only a minor role in skeletal muscle and it is not responsive to exercise. Liver glucose production drops at the later stages of low intensity exercise due to a depletion in liver glycogen concentration. This is the most likely explanation as liver glycogen stores are finite and may become depleted during prolonged (I.e. 2 h of exercise). The liver can still produce glucose via gluconeogenesis but the rate of glucose production is lower than from glycogenolysis. Although there will likely be a drop in total carbohydrate oxidation after 2 hours of exercise, this will be due to muscle glycogen depletion, whereas blood glucose use will be greater than earlier in exercise. Plasma FFA will increase with prolonged exercise, however blood glucose use will be greater than earlier in exercise. Plasma fuel sources become more important in the later stages of exercise as muscle-derived fuels (I.e. glycogen and TAG) are depleted. The rate of gluconeogenesis will likely be higher in the later stages of exercise as noncarbohydrate sources become more important to produce glucose. Plasma FFA are the dominant energy sources at rest The contribution of fat peaks during moderate intensities of exercise with approximately equal contribution from intramuscular triglyceride (IMTG) and plasma FFA. During high intensity exercise the contribution of fat from both sources is reduced During prolonged exercise there is a gradual increase in fat oxidation due to increased utilisation of plasma FFA Energy from fats can sustain us for hours, however it isn't useful during high intensity exercise. A triglyceride has a glycerol backbone and 3 fatty acids attached to it But because the body can't directly oxidise them, they must be broken down first via lipolysis Triglycerides in the bloodstream are called lipoproteins, they can either be low or high, aka LDL or HDL Plasma FFA's float around the bloodstream attached to albumin and are not incorporated to a triglyceride Albumin is a protein made by a liver that circulates the bloodstream and can act as a carrier Skeletal muscle stores triglycerides and gives the muscles FFA's directly. Adipose tissue stores triglycerides and supplies the bloodstream with FFA's Adipose tissue is the fuel store that contains the most amount of stored energy. Glycogen stores can only hold so much and whilst it's important, will only contain enough energy to sustain 90 minutes of exercise An increase in glucagon and a decrease in insulin promotes mobilisation of FFA's from adipose tissue and increase glucose output from the liver. Insulin promotes glucose and fatty acid storage by stimulating glucose transport and storage, and promoting fatty acid storage in triacylglycerol. Therefore, a decrease in insulin concentration during exercise would aid fuel mobilisation. Glucagon promotes mobilisation of fatty acids from adipose tissue and glucose from the liver. Therefore an increase in glucagon with exercise would also aid in supporting fuel availability. On the other hand, an increase in insulin concentration during exercise would aid fuel storage rather than mobilisation. A decrease in glucagon with exercise would supporting fuel storage rather than mobilisation. Insulin inhibits HSL activity 1. 2. 3. 4. Carnitine is compound with a role in cellular metabolism. It supports fatty acid transport into the mitochondria for B oxidation and ATP production. Increases in muscle carnitine results in elevated rates of fatty acid oxidation. Fatty acids need to be transported from the cytosol across the outer and inner mitochondrial membrane into the mitochondrial matrix. This is done through the action of CPT1 which requires carnitine. On the other hand, HSL is activated by catecholamines and muscle contraction but it is not regulated by carnitine. Carnitine is not involved in betaoxidation. Plasma fatty acids are transported into the muscle by CD36 but this is not dependent on carnitine. 4 key steps of fat oxidation Lipolysis in adipose tissue Lipolysis in skeletal muscle FFA uptake into skeletal muscle Transport of FFA into the mitochondria LIPOLYSIS IN ADIPOSE TISSUE Lipolysis is the breakdown of TG into glycerol and fatty acids. This must happen to realise FFA's into the blood and for them to go to the working muscles. Lipolysis is stimulated by the enzyme lipase and lipolysis is activated by exercise There's 2 types of lipases: hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) FFA and glycerol concentrations in the blood rise during exercise. Key drivers for lipolysis is an increase in catecholamines and a drop in insulin LIPOLYSIS IN SKELETAL MUSCLE Occurs similar to step one It is activated by a rise in catecholamines, but also by activated signals in the muscle as a result of muscle contraction. The breakdown of IMTG is specific to type 1 muscle fibres, as in IMTG only decreases in type 1 fibres but not type 2 IMTG content is 2-3 times higher in type 1 and contain a greater level of HSL, ATGL and higher oxidative capacity. Because IMTG are already in the muscle, they can quickly enter the mitochondria to undergo oxidation FATTY ACID UPDATE INTO SKELETAL MUSCLE Plasma FFA's must be transported into the muscle to be used for energy They need to enter the cell via a transporter TG must be broken down into fatty acids in order to cross the cell membrane. TG is broken down by lipoprotein lipase Most FFA's are transported in the blood are bound to albumin. For the FFA to go into the muscle, it must unbind from the albumin The FFA must pass the membrane via a transporter There's 3 transporters: FAT/CD36 (transporter for fat acid entry into the cell), FABPpm (fatty acid binding protein is a transporter ON the cell membrane) and FATP (fatty acid transport protein in another fatty acid transporter allowing the uptake of fatty acids in to the cell) One FFA's are in the cell they will either be turned back in TG and stored as IMTG or they will enter the mitochondria to undergo oxidation and ATP resynthesis. During exercise FFA's are directed towards the mitochondria and away from storage as IMTG FATTY ACID UPTAKE DURING EXERCISE Increases of plasma FFA oxidation during exercise is only possible due to an increase in the uptake of FFA into skeletal muscle The increases in exercise lead to an increase in FFA uptake due to the movement of FFA transporters from inside the cell to the membrane FATTY ACID TRANSPORT INTO MITOCHONDRIA The final step FFA's from plasma and IMTG must enter the mitochondria to undergo oxidation and then undergo aerobic metabolism to make ATP Carnitine proteins help to transport fatty acids across the mitochondrial membranes Fatty acids get activated and become fatty acid acyl-CoA to be prepped for oxidation Fatty acid acyl-CoA joins carnitine to form acyl-carnitine. This can then pass through the mitochondrial membranes into the matrix The carnitine is then removed and it goes back to fatty acyl-CoA, which can then undergo oxidation MODULE THREE: OXYGEN DELIVERY Topic 3.1 Focus for this topic is understanding how O2 is delivered to the working muscle at a sufficient rate to support aerobic ATP resynthesis 3.1.1 Overview of Oxygen Uptake and Exercise Video Notes Rate of oxygen uptake is measured in L/min VO2 is the term used to describe it Oxygen consumption is related to oxygen demand At resting conditions, O2 requirements are low. With an increase in O2 demand is an increase in O2 utilisation. Increases in O2 demand leads to an increase in O2 consumption Max oxygen uptake aka VO2 max. Oxygen uptake reaches maximum and plateaus despite any increases in exercise intensity. There is a linear relationship between oxygen consumption and exercise intensity. As much contraction increases, so does the demand of oxygen in aerobic metabolism. The heart has a primary role in delivering O2 during exercise. We also need an increase in ventilation to sustain enough O2 in the blood to the working muscle. Our CV system needs to work to balance out O2 and CO2 Fick equation: VO2 = cardiac output and (a - v O2 difference) CO is the amount of blood pumped by the heart. A-v O2 difference. This is the difference in oxygen content in the arterial and venous systems Oxygen uptake in exercise increases due to: increased delivery of O2 to the active tissues (Increased cardiac output and redistribution of blood flow from non essential systems during exercise) and increased O2 extraction by the active tissues (increased recruitment of capillaries and increased activity of mitochondrial enzymes) CO = HR (bpm) x SV (L)(volume of blood pumped with each beat) CO is the amount of total litres of blood pumped by the heart every minute HR increases with exercise intensity, there is a set max point for HR. HR is controlled by the SA node and AV node. These nodes are linked to the sympathetic and parasympathetic system. The PNS works as a 'break' to slow heart rate. When stimulated, the vagus nerve releases acetylcholine which decreases the SA node and decreases HR The rise in HR during exercise is a result of withdrawal of PNS activity. SNS increases HR during moderate-high intensity exercise. The sympathetic nerves release adrenaline and noradrenaline, which then act on receptors on the SA and AV nodes to increase HR. HR increases through fight or flight response. Beta blockers slow heart rate, they compete with the adrenaline/noradrenaline by binding with receptors to prevent the SNS action. Stroke volume increases during exercise but only to a certain point. About 40-60% of VO2 max, at least in untrained individuals. The reason for the set point is because due to the higher heart rate, there is a decrease in the amount of time the ventricles can fill. However in endurance trained athletes, it can continue to increase. In trained athletes, there is improved ventricular filling during heavy exercise due to increased venous return. Factors affecting SV: end diastolic volume, average/mean arterial pressure and strength of ventricular contraction. MAP: changes in pressure is the reason that it flows the correct way. Increased pressure will reduce the amount of blood that can be ejected and thus, reduce stroke volume. MAP continues to rise during exercise, but is counteracted by the increased contractile force of the heart and dilation of the arterioles. Contraction strength: increases are enhanced by increased concentrations of catecholamines. This release enhances calcium release and cross bridge cycling. EDV: volume of blood in the ventricles in the relaxation phase aka diastole phase. The strength of ventricular contraction is larger when the ventricles are stretched = larger EDV, lengthened cardiac fibres and the strength of contraction is greater. This is known as the Frank-Starling Effect. Venous return is the main determinant of EDV. Venous return: this is enhanced by: 1. Venoconstriction: the SNS can decrease the diameter of the veins returning blood to the heart. This increase in pressure forces more blood to return to the heart. 2. muscle pump: muscle contraction exerts a rhythmic pressure on the vessels and forces blood along the vessel towards the heart. 3. Respiratory pump: in inspiration, the diaphragm moves down to expand the lungs and decrease pressure, this helps facilitate venous return. During exercise, blood flow increase to skeletal muscle, but only the ones that are working. For more blood flow to be directed here, there needs to be a decrease in flow towards other organs. This is mostly the organs of the digestive system, as they're not needed during exercise. CO delivered to the heart is similar during exercise, but blood flow increases. CO to the brain is lower but the volume of blood is maintained or increased. CO to muscles increase from 20% > 80% during exercise Blood flow to the digestive system reduces from 20% to 5% Skin blood flow typically increases, but may drop during maximal exercise. In the short term, this is ok but can be problematic in the long term. 1. The exchange of O2 from the blood into the muscle occurs in the capillaries – single cell thick vessels were O2 diffusion is quick and easy 2. The arteries and arterioles that supply the capillaries are surrounded by smooth muscle. 3. Contraction of the arterial smooth muscle causes a reduction in the diameter of the blood vessel – termed vasoconstriction. This increases resistance and reduces flow. 4. Relaxation of the arterial smooth muscle causes an increase in the diameter of the blood vessel – termed vasodilation. This reduces resistance and increases flow. 5. At rest, only 50% of the muscle capillaries are supplied with blood due to vasoconstriction of the arterioles supplying the capillaries. During exercise, increases in blood flow to contracting muscle is due to vasodilation of the resistance arteries and of the arterioles. Vasodilation of resistance arteries reduces resistance in the vessels and increases blood flow to skeletal muscle. Increased flow only goes to the contracting muscle. This is linked to the metabolic needs of the muscle and also relates to the degree of motor unit recruitment and demands of muscle contraction. (think size principle). Muscle factors control its own blood flow, this is termed autoregulation. There is vasoconstriction in inactive tissues during exercise. Composition of blood Haematocrit: % of blood that is made up of cells. Plasma: mainly water, but contains proteins, hormones and metabolites WBC and platelets: fight infection and clotting factors that stop bleeding. RBC's: cells containing O2 carrying protein haemoglobin. CARDIOVASCULAR RESPONSES TO EXERCISE At the onset of exercise, there's a rapid increase in CO, driven by HR and SV If exercise intensity isn't high, then SV and HR will plateau within minutes. Return of CO to baseline following exercise depends on: exercise duration and intensity, exercise in hot and humid temperatures and training state of subjects. In incremental exercise: CO will plateau and Increases in MAP is due to rising in systolic BP, as diastolic BP is relatively unchanged. In prolonged exercise: CO is maintained, this is needed to ensure adequate oxygen delivery to meet the workload demand. As it progresses, there's a decline in SV and CO is maintained. This is termed cardiovascular drift. The fall in SV is due to a decline in EDV. Declines in EDV can be from gradual fluid lose and increases in body temperature. Gradual fluid loss causes a drop in plasma volume and thus there's a lower volume of blood circulating. Increased body temp causes a redistribution of blood flow and creates a competition between the working muscle and the skin. Increases to skin will reduce the volume of blood returned to the heart. Regulation of CV responses to exercise HR response at the onset of exercise is almost immediate. This is due to central command. It works to initiate and coordinate cardiac responses to exercise. Motor signals from the motor cortex stimulate muscle contraction and movement. The higher brain centres are also linked to the CV control centre, controlling HR and blood flow. When a motor signal is generate for the muscle, it is also sent to the CV centre to generate a response. When we transition from low intensity to higher intensity, we need larger CV responses to increase O2 delivery. There are higher motor signals generated to give a greater response for the muscles and for the CV control centre. There is a recruitment of larger motor units and an increase of O2 to the working muscles. During exercise, when the motor cortex produces a signal and sends it out, it invokes vasodilation of the working muscle and vasoconstriction to the non essential muscles/organs. The HR will increase to help compensation for a decline in SV. Afferent feedback: signals sent from the peripheral to regions in the brain. During exercise, things that provide feedback are: muscle chemoreceptors that are sensitive to change in the intracellular environment, eg: changes to H+ and lactate, mechanoreceptors that are sensitive to changes in force and speed of muscle contraction and movement and baroreceptors that are sensitive to changes in arterial blood pressure. Increased oxygen delivery to the working muscle during exercise is driven by increases in cardiac output and a redistribution of blood flow from inactive to active tissues. The increase in heart rate occurs via the autonomic nervous system whereas increased stroke volume is determined by a combination of contractility, end-diastolic volume and mean arterial pressure. Local factors derived from the skeletal muscle increase blood flow to active tissues during exercise Cardiovascular responses to exercise are initiated by higher brain centres and largely aligned with the magnitude of muscle mass activation Cardiovascular responses are fine-tuned through feedback from various receptors sensitive to movement, biochemical and pressure changes Muscle metabolites produced by contracting muscle stimulates vasodilation and an increase in blood flow to the contracting muscle. Topic 3.2 Cardiac output is not always higher in endurance trained individuals, compared to untrained individuals. It's related to the O2 requirements of the activity. It should be similar between the individuals as the O2 demands would be the same. When working at max workload, this is different. Stroke volume is higher and heart rate is lower in endurance trained individuals than untrained at all times. This is due to cardiovascular adaptations. Improved SV is due to changes in the heart and some vascular adaptations also. Factors affecting SV: contraction strength, MAP and EDV. At submaximal exercise, endurance trained individuals will have a lower heart rate and higher stroke volume than untrained individuals At maximal exercise, endurance trained individuals have a higher maximal cardiac output due to elevated maximal stroke volume. The increased stroke volume is due to a combination of central adaptations occurring in the heart as well as peripheral factors in the blood and the vascular beds. Topic 3.3 How O2 is delivered to a muscle and changes to respiration are different things. The respiratory system changes in demand to exercise and needing greater oxygen availability. Pulmonary ventilation (Ve) (L/min) = breathing rate (breaths per minute) x Tidal volume (L per breath) Pulmonary breathing enhances during exercise During the onset of exercise, there's small changes to the amount of PO2 and PCO2, which stimulates ventilation During incremental exercise, Ve will rise in a linear fashion up until about 50-75% of VO2max, above this, It becomes non linear, this is termed ventilatory threshold. Regulation of Ventilation Video Notes Ve increases at the onset of exercise and is proportional to the intensity of exercise. The respiratory system has a control centre in the brain > the medulla oblongata. The medulla oblongata controls both the inspiratory (diaphragm and external intercostals) and expiratory muscles (internal intercostals and rectus abdominis). Expiration relies on passive stretch of the lungs The respiratory system relies on a feed forward system. The higher brain centre controlling movement, will also initiate a response in the respiratory control centre. Afferent neural feedback can come from mechanoreceptors that detect stretch and movement of the lungs. Most feedback comes from chemoreceptors throughout the body: changes within the brain step and uptake of PCO2 and H+ in the cerebrospinal fluid. In the peripheral, chemoreceptors in the aortic arch and carotid bodies, changes in PCO2, H+, K+, adrenaline, temperature and a drop in PO2. Chemoreceptors in skeletal muscle detect rising levels of K+ and H+ Ventilation rate is sensitive to changes in arterial PCO2, detection of it has a key role in changes to ventilation. Changes to PO2 doesn't effect ventilation until it drops to 70 mmHg and it's picked up by receptors in the carotid bodies. Ventilation - High Intensity Exercise When we jump from moderate to high, ventilation stops following a linear pattern, despite O2 requirements still remaining the same. Anaerobic Threshold The common theory for the non linear increase in Ve is that the increased generation of lactate from higher levels of glycolysis leads to increases ventilation. It's not from an increase in lactate concentration, but an increase in H+ in the blood and CO2 in the pulmonary circulation. This is stimulate chemoreceptors to buffer the blood Additional Factors to increased ventilation Motor unit recruitment and neural input: because muscle motor recruitment isn't linear, this could have an effect on ventilation. Blood potassium (K+) concentrations: K+ rises in the blood during high intensity exercise which will stimulate muscle chemoreceptors. Catecholamines and rising body temperature: also just known to stimulate ventilation Hypoxia: not a factor. Gas Transport: Diffusion of Gases Reminder: O2 is delivered by cardiac output and blood flow, it is used via oxidative phosphorylation Partial pressure of gas is determined by the % of the gas and the barometric pressure Diffusion is determined by: the diffusion area, how easily a molecule diffuses The difference in partial pressure of the gas on each side of the tissue (diffusion gradient) The thickness of the tissue The lungs are designed for diffusion. We need to maintain a diffusion gradient to ensure transfer of gases across the different tissues. Oxygen Transport O2 in the body is either dissolved in solution of carried in red blood cells. Any that's dissolved is called PO2, but this only makes up 1%. Most O2 is bound to haemoglobin. Each Hb molecule can carry 4 O2 molecules. O2 needs to unload from Hb to diffuse into the tissues. O2 - Hb Dissociation Cure Video notes O2 can both bind and unbind from Hb. When there's high levels of PO2, this results in the O2 to bind to Hb and thus, an increase in oxygen saturation. When there's a decrease in PO2, they will unbind to increase PO2 and unsaturate Hb. During intense exercise, there is a drop in PO2 Impact of exercise: 1. Changes in pH – an increase in the concentration of H+ in the blood reduces the O2 carrying capacity of haemoglobin. Therefore during intense exercise when there is an increased production of H+, there is a greater unloading of O2. 2. Changes in temperature – during exercise an increase in heat production in the working muscle will also cause a rise in the temperature in the blood. A rise in temperature weakens the bonds between O2 and Hb, again causing greater O2 unloading during exercise. Oxygen Transport in Muscle Myoglobin is a similar protein to haemoglobin but is present in cardiac and skeletal muscle. It acts to store O2 within muscle and can buffer the O2 requirement of the muscle at the onset of exercise while O2 delivery is being increased. It also transports O2 from the cell membrane to the mitochondria – where it is required to accept electrons at the end of the electron transport chain. Myoglobin has an even higher affinity for O2 than haemoglobin, It only offloads at very low PO2 and will hang on to it until the mitochondria need it. Carbon Dioxide Transport Can be done in 1 of 3 ways: dissolved in plasma, bound to haemoglobin or as bicarbonate. When PCO2 is high, it binds with water to form carbonic acid, which is catalysed by carbonic anhydrase in the RBC. It then dissolves into the bicarbonate and H+, it's then diffused out of the RBC and into the plasma. Endurance Training, Ventilation and Pulmonary System A period of endurance training will reduce the ventilatory response at the same workload. This is possibly due to lower H+ production = less afferent feedback from the chemoreceptors. Lactate accumulation is also lower after training due to enhanced oxidative capacity and a shift towards fat instead of carb oxidation Endurance training doesn't change the physical size/capacity of the lungs. Topic 3.4 VO2max is defined as: the maximal rate at which oxygen can be transported to and consumed by the body's tissues Rate is L/min. can be expressed as an absolute rate or relative to body weight. VO2max will vary between individuals. Those that are endurance trained can have almost double the VO2max value than someone sedentary. Having a high VO2max is important for health. It is a better predictor for death than other risk factors. Methods of Assessment of VO2max (video notes) VO2max is relevant for both endurance athletes and is a useful clinical tool to assess risk of other diseases Test 1: incremental exercise test: whole body exercise, increased work rates every 1-3 minutes, specific to athletes sport. In order to get a true value of VO2 max, you look for a plateau in VO2 despite increasing workload. Other measures: blood lactate, RER, HR within 10bpm of age predicted max It can also be predicted from sub max tests. Physiological Determinants of VO2max VO2max integrates multiple systems 4 systems responsible for delivering and utilising O2: pulmonary diffusing capacity, cardiac output, O2 carrying capacity and skeletal muscles 1. The respiratory system: possible limitations to VO2 max such as: ventilation rate, lung perfusion (blood flow to the lung), Hb-O2 affinity and O2 diffusion. In most people, there isn't a respiratory limitation as in most condition, oxygen saturation is mostly well maintained. Increasing oxygen availability doesn't have an effect on O2 saturation and VO2max. Saturation can drop in hypoxic settings, individuals with respiratory limitations may experience low VO2max. 2. Cardiac output: there's strong positive relationship between CO and VO2max. Reduction in cardiac output has shown decreases in VO2max. 3. Oxygen carrying capacity: this is determined by the Hb content. RBC volume is closely related to VO2max. If you infuse more blood into the circulation, this elevates O2 carrying capacity of the blood, this will increase VO2max by up to 10%. This is blood doping. 4. Skeletal muscle: site of O2 consumption. Mitochondria are the sites of O2 consumption, O2 is used at the end of the electron transport chain to help generate ATP via aerobic metabolism. Mitochondrial increases don't correlate well with improvements in VO2max. Capillary density has a good relationship with VO2max. Elevated capillary density increases blood transit time and reduces diffusion distance for O2, this is important for O2 extraction. VO2 max is frequently referred to by the Fick Principle which states that VO2 is a function of both oxygen delivery (cardiac output) and the amount of oxygen extracted – which is the difference between O2 content in the arterial and venous systems (arteriovenous O2 difference). Increases in either variable would increase VO2max. Well, the general consensus now is that the main limitation to VO2 max is central and determined by maximal cardiac output. Other factors determining VO2max: body size, biological sex (females have a typically lower VO2max), aging and genetics. Endurance training done 3+ times per week can increase VO2max. The amount of improvement is dependent on the duration and intensity of exercise program and the VO2max at baseline. MODULE FOUR: ENVIRONMENTAL PHYSIOLOGY Topic 4.1 It is important for an EP to have an understanding about how environmental conditions affect not only athletes, but those in other professions as well. Body temperature is kept within a narrow range to ensure survival. This is because our body can only perform functions within a certain temperature. When body temp increases above 45, it can stop the adequate functioning of proteins and enzymes and lead to ATP generation failure. Opposite that, temp below 34 can cause arrythmias and also lead to death. Regulatory mechanisms are at work constantly, but can be challenged by prolonged exercise. Especially in hot conditions. To remain stable, our body needs to match heat production with heat loss. Metabolic reactions involved in ATP resynthesis generate heat. At rest and during sleep, we make heat via basal metabolic reactions. Vo2 values are about 0.3L/min, but cause heat generation is small, heat loss is small. 20-30% of energy in foodstuff goes to ATP, the remaining of energy is lost as heat. Heat Production (voluntary): During exercise, metabolic rate and heat production from metabolism can increase 10 fold, compared to resting conditions. 70-80% of energy expended during exercise is lost as heat, but during exercise the heat load can be high. Prolonged exposure to high heat can harshly challenge our cooling mechanisms. Heat Production (Involuntary): shivering is our body's way of generating heat when cold, this can increase heat production 5 fold. Non-shivering thermogenesis is when our metabolic rate is enhanced, due to an increased concentration of thyroxine and catecholamines. Types of Heat Loss 1. Radiation: in the form of infrared rays. Transfer of heat from surfaces that not in contact. This makes up 60% of heat loss. Heat can be gained or lost depending on the conditions. 2. Conduction: transfer of heat between objects in contact with each other. The direction will depend on the temperature of the objects. 3. Convection: heat is transferred to air or water in contact with the body. Eg: feeling a fan move cool air across the body. 4. Evaporation: heat is transferred from the body to water on the skin surface. This only accounts for 25% of heat loss at rest, but is the major form of heat loss during exercise. This type of heat loss depends on ambient conditions, convective currents around the body and skin exposure. Video notes: During exercise in a cool environment at sub max, heat loss is primarily via evaporation. There are small contributions via convection and radiation. With increases in exercise intensity, there is a linear increase in heat production and body temperature. With this, there is an increase in evaporative heat loss that overshadows other heat loss mechanisms. When there is an increase in air temperature, if you keep the same intensity of exercise, there is no change in heat production, there is an increase in evaporative heat loss, but a decrease in convective and radiant heat loss. Topic 4.2 Video Notes Changes in hormones: in the control group there is a slight change in adrenaline, however when you exercise in heat, there is a higher rise in adrenaline. Changes in CVS in heat: sweat production, increased evaporative heat loss, higher amount of sweat loss which can increase a risk of dehydration. Evaporation is good at maintaining core temp but does increase risk of dehydration. During exercise in heat, skin temperature increases due to blood flow rushing to the skin, which is carrying heat. the decrease in blood return to the heart then reduces stroke volume. Circulatory conflict: competition between the skin and contracting muscle blood flow. Increased skin flow takes blood away from the working muscle. Increased skin blood flow reduces central blood volume and venous return. In order to maintain CO and SV, heart rate has to increase to keep up. High core temperature and catecholamines increases heart rate during exercise in the heat. dehydration can occur due to loss of fluid and rise in core temp. this can impair cardiac output at around 3% dehydration. Respiratory: ventilation is higher during exercise in the heat. CO2 is the driver of changes in increases in respiration. But PCO2 in blood doesn't change during heat, it's not the driver of change during exercise. Elevated core temp and plasma adrenaline go up during exercise and trigger the respiratory centre in the medulla Metabolism: elevated RER due to increases in carbohydrate oxidation. Exercise in heat uses higher rates of muscle glycogen, but not much change to other fuel stores. There is an increase anaerobic glycolysis and elevated muscle and blood lactate levels. there is elevated blood glucose due to increases in liver glucose output (liver glycogenolysis). During exercise in heat, the liver breaks down glycogen and pumps out more glucose, it's a stress response. If muscle started taking up glucose, then blood levels wouldn't change. In both hot and cold conditions, the muscles take up the same amount of glucose. Single sprint performance is better in warmer conditions. Due to local muscle heating, active warm ups, higher core temp, etc. There's likely improved contractile protein function as a result, greater anaerobic ATP production and possibly faster AP conduction. Prolonged Sub max exercise This is impaired in hot conditions. With the time to fatigue being earlier. Mechanisms of Fatigue Fatigue in hot conditions occurs when critical temperature is reached. When repeated training in hot conditions, the body begins to adapt and time to fatigue is longer. Potential factors of fatigue in heat: accelerated muscle fatigue, cardiovascular functions and CNS dysfunction. Accelerated muscle fatigue: muscle glycogen breakdown and lactate production increase in hot conditions. Whilst muscle glycogen depletion is unlikely to be the cause, other causes may be: interrupted excitation contraction coupling, impaired mitochondrial function and enhanced muscle damage Cardiovascular Function: due to circulatory conflict between the skin and muscles, the reduced blood flow to the muscles could reduce oxygen delivery and create the onset of fatigue. Unlikely however in low intensity exercise. CNS dysfunction: high body temp can reduce central drive from the motor cortex and cause fatigue due to a reduction in motor unit recruitment. This causes fatigue in force production from the muscles. A likely mechanism in prolonged sub max exercise. Topic 4.3 Cooling can be done before or during exercise. Precooling: the aim is to lower core temp prior to exercise, this allows the athlete to work more before the onset of hyperthermia Percooling: the aim is to enable greater heat loss during exercise and help delay a rise in core temp. Methods of cooling: cooling vests, cold water immersion, cold water/ice slurry ingestion and cooling packs. There is evidence backing the effectiveness of cooling techniques Heat acclimation or acclimatisation is a strategy used to help improve performance in the heat. Acclimatisation refers to changes occurring after months or years of heat exposure, acclimation is a short term adjustment. Techniques for heat: passive heating, exercising and regular exercise in the heat. Adaptations: reduced body temperature, reduced HR during exercise, increased plasma volume, increased sweat rate, earlier onset of sweating, lower sweat sodium loss, reduced muscle glycogen utilisation and enhanced endurance performance. Full heat adaptation can take up to 2 weeks for some adaptations, exercise bouts of about 1.52hrs seem most effective for the induction of heat acclimatisation. Heat acclimatisation is best done with strenuous interval training or continuous exercise at >50% of maximal oxygen uptake for at least 1hr every 3 days. Heat adaptations can fade. HR and plasma volume will adjust first within a few days, but sweat rate can take up to a few weeks. To help reduce hyperthermia during prolonged exercise in heat, doing a 2hr training session every other day for the 10 days prior to the event can help. Topic 4.4 Fluid loss occurs during exercise The human body is mostly water. Most of the water is within cells of the body, only a small amount circulates in the blood. ECF is about 5% plasma volume and 15% interstitial fluid Plasma volume decreases 10-15% at the onset of exercise: (not due to dehydration) fluid moves from plasma to the contracting muscle due to hydrostatic pressure As exercise continues, there is further fluid loss due to sweating The loss of plasma impacts our ability to thermoregulate Haematocrit: if someone has a haematocrit of 42%, it means that the RBC is taking up 42% of a blood test when they spin it and split the RBC and the plasma During exercise haematocrit can be used to calculate plasma volume In the first 30 mins of exercise, haematocrit increases due to the movement of fluid and this level increases due to further fluid loss Fluid Loss, Dehydration, Physiological Responses and Exercise Performance Once you loss more than 3% body weight, performance starts to become impaired Dehydration has impacts on thermoregulation, hormone responses, CV responses and energy substrate utilisation Dehydration will also impact performance There is a decline on CO when someone is dehydrated. About 90 mins in, there is a significant drop in CO. There are increases in adrenaline and noradrenaline when dehydrated. There are major declines in performance if you are already dehydrated. (this was based on endurance training) Dehydration also has impairments on muscle power in wrestlers. In a hydrated state, there was greater muscle power. Dehydration can reduce central blood volume, leading to reduced venous return and therefore, reduced stroke volume. Since cardiac output is the product of stroke volume and heart rate, a reduced stroke volume would likely lead to reduced cardiac output, particularly at high-to-maximal exercise intensities. Exercise when dehydrated can lead to increased blood glucose levels mainly due to liver glycogenolysis. The breakdown of liver glycogen is increased in a dehydrated state, leading to output of glucose into the bloodstream and a rise in blood glucose levels. Summary If you start dehydrated and exercise, the following occurs Increases in: core temp, catecholamines, heart rate, muscle glycogen use and lactate Decreases in: blood volume, stroke volume and cardiac output. Topic 4.5 Video One Ingesting fluid during exercise can help prevent dehydration and has effects on thermoregulation, hormone responses, CV responses and energy substrate utilisation The more fluid you drink during exercise = smaller increases in core temperature. Adequate fluid will also minimise impacts on CV output Not enough fluid will increase adrenaline which increases glycogen use during exercise if you have enough fluid, you will lose less glycogen. There is a reduced reliance on anaerobic glycolysis Adequate fluid helps to prolong fatigue Summary With fluid replacement Increases: blood volume, stroke volume, cardiac output and improved exercise performance Decreases: core temp, catecholamines, heart rate, muscle glycogen use and lactate. Video Two You need to ingest enough fluid to minimise dehydration. Enough to balance out fluid loss. Complete rehydration needs to occur prior to following competition and training Fluid requirements is going to vary between people and sometimes you can't ingest enough fluid during exercise. Some people make sweat a lot and cannot drink all the fluid requirement to compensate for it. Sweat is hypotonic, so water is more important to get in then electrolytes. Adding things to water can be beneficial. Sodium can be beneficial and carbohydrate (but to a point). There's 3 key sites of fluid ingestion during exercise: rate of ingestion, rate of gastric emptying and rate of intestinal absorption. The volume and composition of a drink will impact these too Rate of ingestion factors: palatability (temp, flavour and sweetness) (there is science behind this. If not dehydrated, Gatorade doesn't taste as good if you're dehydrated) and access to fluid. Those that drink voluntarily will only get in about 50% of what they're lost and getting in 1-2L of fluid per hour can be very difficult. Rate of gastric emptying factors: volume ingested, carbohydrate concentration and osmolality. Larger volumes of fluid will stretch the stomach more = higher rate of gastric emptying into the intestine. If you change the amount of glucose in a drink, there tends to be more left in the stomach and not released into the small intestine. Any higher than 6-8% carbohydrate will slow gastric emptying. The amount of salt in the drink won't impact the stomach. Rate of intestinal absorption factors: water absorption occurs via osmosis. For fluid to be better absorbed, there should be a bit of carbohydrate and electrolytes. Only needs to be small. Too much carbohydrate will impair absorption. Instead of the fluid going into the intestine and into the blood, it puts the fluid back into the intestine and can result in diarrhoea Video Three Following exercise: ADH hormones will release to help reabsorb water (renin and aldosterone). These help to promote water and sodium retention in the kidneys The ingested amount of fluid needed should be greater than sweat loss and have some sodium in it. Having higher volumes of fluid with a bit of sodium appears to be the most beneficial. Sometimes higher levels of sodium can be beneficial. Sodium consumption has a positive effect on returning plasma levels to normal following exercise.