KIN 202 Exam Review PDF

Acute exercise – something performing a single bout of a type exercise - Leaving house a biking for 60 minutes - Aerobic or endurance that is supramaximal - Sprinting: supramaximal effort - High intensity intervals: 80% or above heart rate - Resistance: places much greater mechanical...

Acute exercise – something performing a single bout of a type exercise - Leaving house a biking for 60 minutes - Aerobic or endurance that is supramaximal - Sprinting: supramaximal effort - High intensity intervals: 80% or above heart rate - Resistance: places much greater mechanical load on muscles that is normally encountered during daily activities Chronic exercise – repeated bouts over a given period of time. - Can be short term or long term (weeks or months) - Aerobic or endurance repeated typically 12-24 hrs - SIT: supramaximal followed by low intensity recovery period. Less than 60 minutes of recovery time between exercise - HITT: repeated high intensities intervals followed by low intensity recovery. Less than 60 mintues - Resistance: repeated bouts. Typically 12-24 hr between exercise bouts Incremental/progressive exercise test – exercise intensity increases. Protocol set in place Steady state – moderate intensity exercise when the removal of lactic acid by oxidation keeps pace with its production. Oxidation phosphorylation is primary atp supply. Work rate is set and the individual is to pedal for that time or until tired. Interval / intermittent – several periods or predefined exercise is separated by predefined periods of rest Absolute value – can be applied to every and expressed in standard unit. Relative value – one that has been normalized to a specific known for a unique individual. Cycling at 60% of VO2 max. 1 HEART = 2 PUMPS Left = systematic circulatory Right = pulmonary circuit Cardiomyocytes – bulk of the myocardium What determines if a valve open or closed? - The pressure gradient - Heart conveyes energy to the blood in the form of pressure which = blood flow from high to low pressure Cardiac cycle - Repeats relaxation and contraction - Two step pumping: atria and ventricles contract/relax out of phase - Atria contracts before ventricles - Systole (0.3 seconds)= contraction - Diastole (0.5 seconds) = relaxation - One full cardiac cycle lasts 0.8 seconds at rest - 0.2 systole and 0.13 diastole which is 0.33 seconds at heavy exercise Pulmonary and systematic circulation: 2 pumps, 2 distinct vascular networks – each network has arterial (higher pressure) and venous (lower pressure) circulation Pulmonary arterial systolic and diastolic pressure: lungs Systematic venous pressure: everything else Central venous pressure: venous blood pressure in the venous cava near the right atrium. CVP influences filling of atria and subsequently the ventricles Systematic arterial pressure Systolic blood pressure – pressure blood exerts on the walls of large arteries during systole Diastolic blood pressure – pressure blood exerts on the walls of large arteries during diastole Normal range 120/80 mmhg Mean arterial pressure – time arranged arteriole blood pressure over an entire cycle. MAP = 90 mmhg Pulse pressure = systolic pressure – diastolic pressure Mean arterial pressure = diastolic pressure + 1/3 pulse pressure - As blood travels through the systematic arterial circulation it encounters smaller and smaller vessels which increases the resistance to flow and some energy in the blood is lost. Resulting in a decrease in pressure 3 layers Media: smooth muscle, collagen, elastic Adventitia: collagen, fibroblasrs, nerves, vasa vasorum Intuma: endothelium Diffusion rate J = between 2 reference points D = constant characteristic of specific medium through which diffusion is occurring C = difference in concentration X = difference in distance A = surface acrea - A high diffusion constant, high concentration difference and low diffusion distance and favour a high rate of diffusion Factors that influence MAP MAP = CO x TPR Hemodynamics: the relationship between blood flow, pressure and resistance Blood flow: pressure / resistance - There must be a pressure difference to drive blood flow – flow will be directly proportional to the pressure difference across a vascular network in a tissue - The heart pump conveys energy to the blood in the form of pressure - With a even pressure head, blood will tend to distribute the most to areas where the resistance to flow is low - Flow will be inversely proportional to resistance - The vascular system provide the resistance to flow What is the driving pressure in the systematic circulation? MAP = CO x TPR Map: the blood pressure in the large arteries time-averaged over the entire cardiac cycle TPR (total peripheral resistance) – the sum of the resistance to flow provided by all of systematic blood vessels Individual blood vessel , resistance is determined by: - Viscosity of blood - Viscosity is the internal resistance to flow of a fluid - Viscosity is determined by hemocrait (the % by volume of red blood cells in given volume of whole blood) - Length of blood vessels - Radius of blood vessel Factor most important in determining acute changes in resistance to flow through a blood vessel - Radius - 2 x increase in L = 2 x increase in radius - 2 x increase in r = 16 x decrease in radius What effect would this have on blood flow through the blood vessels? - Increase in radius = decrease of resistance = increase in blood flow  - Decrease in radius = increase in resistance = decrease in blood flow Factors that regulate vascular tone and thus control blood flow Neural - during exercise, SNS activity increase and intensity/duration increases. - In general , SNS stimulation of vascular smooth muscle will cause vasoconstriction Tissue metabolism - Metabolites are produced in skeletal muscle cells - Metabolites diffuse or are extruded from the cell and the concentration of the metabolites increase in interstitial fluid. - Concentration of metabolites in the ISF is proportional to metabolic rate - Vasodilatory effect is proportional to the concentration of metabolites in the ISF Isoforms – highly related protein that have very similar amino acid sequence and essentially the same biological function. Protein activity (enzyme activity) – the rate (speed) at which a protein performs its function Activity determined by - Chronic change 1. Protein expression 2. Protein – protein interaction 3. Phosphorylation 4. Redox modification 5. Allosteric modifiers Protein activity is not a “set” value, it changes under different cellular/metabolic conditions - Typically a resting / basal activity - Protein activity can increase or decrease in basal Primary functions of skeletal muscle - Generate force - Fuel storage: major site for amino acids (protein), glucose (glycogen), fat (triglycerides). - Temperature regulation - Force / shock absorption Muscle anatomy Muscle cell = muscle fiber Cell membrane = sarcolemma Cytoplasm = sarcoplasm Endoplasmic reticulum = sarcoplasmic reticulum - Approximately 250 myosin molecules joint to form 1 thick filaments - Each thick filament is arranged so the myosin heads are clustered at the ends and central region is a bundle of myosin tail - 1 myosin = 2 myosin proteins - On 1 myosin hinge region there are 2 light chains which are RLC and ELC - Only 1 troponin complex for every 7 actin monomers in a thin filament Thin filament proteins ACTIN - Composed of small globular subunits (G actin) that form long strands of Fibrous actin - Each G actin protein contains 1 active site to which myosin heads will bind during contraction - Actin filament formed by 2 strands of F actin in a coiled coil TROPOMYSON - Long, rod-shaped, double-stranded, helical protein that is wrapped about the long axis of the actin backbone TROPONIN - Complex of 3 proteins - Troponin T, I and C ( tropomyosin-binding, Inhibitory and Calcium binding) Sliding filament theory of muscle contraction Huxley - the length of A band of a sarcomere remains constant during contraction and the shortening of the myosin molecules could not be responsible for contraction Sliding filament theory: - overlapping muscle filaments of fixed lengths (thick and thin) slide past each other in an energy-requiring process to result in muscle contraction Excitation-contraction coupling: - Membrane potential is determined by concentration gradient of Na, K, Cl and the sarcolemma permeability to these ions - -70mV on the inside of cell compared to outside - An action potential arrives at the axon terminal, causing voltage gated Ca channels to open. Calcium entry causes synaptic vesicles to fuse with the presynaptic membrane and release Ach into the synaptic cleft  - T- tubules are extensions of the cell membrane (sarcolemma) that associate with the ends (terminal cisterna) of the sarcoplasmic reticulum Sarcoplasmic 3 functions - Ca 2 storage - Ca release during excitation - Removal of Ca from cytosol when excitation ceases Crossbridge cycle 1. Atp irreversibly binds to strongly bound action-myosin 2. Atp binding causes myosin to detach from actin and depending on the Ca concentration the process can continue or cease 3. Atp hydrolysis: energy released cause the myosin head to swivel into cocked position 4. Myosin can bind weakly to actin (or there can be no actin-myosin interaction), but in the absence of Ca 2 Tm sterically blocks access of the myosin head to strong binding sites on actin. 5. Binding of Ca to TnC overcomes the inhibitions of TnI, movement of Tm filament, which exposes strong binding site on actin. 6. Release of Pi products results In the power stroke 7. Strain-dependent isomerization (irreversible step in cycle) 8. ADP is released, which results in the rigor state Pi release = trigger power stroke ADP release = allows ATP to rebind after completion of power-stroke ATP binding – loosens myosin head from actin ATP hydrolysis – energy used to reverse power stroke EC coupling 1. Action potential from alpha neuron arrives at axon terminal and causes acetylcholine release 2. Ach binds to nicotinic receptors, causes the muscle fiber to depolarize and creates muscle action potential 3. Muscle action potential travels along sarcolemma and down into t-tubules 4. Depolarization of the sarcolemma / t-tubule membrane activates DHPR, which is physically linked to the RyR 5. DHPR activation results in RyR opening (Ca2 channel) and Ca diffuses out of the SR into the cytosol 6. Ca will bind to TnC and due to conformational changes in TnC,TnI and TM the myosin binding site on actin is exposed 7. Myosin heads can now strongly interact with actin 8. EC-coupling and the cross bridge cycle will continue as long as the muscle fibreis excited Relaxation. What needs to happen for a muscle to relax? 1. Excitation must cease 2. Membrane repolarization (K channels open and K leaves) and the Na and K concentration gradient must be restored (Na+/K+ ATPase) Na out and K in. K leaves cell to bring back to -70mV. 3. Cytosolic Ca2 concentrations must be stored to normal (50-100mm). SECRA takes calcium and sends it to lumen centre of SR. Goes against gradient. Motor units - Motor unit = motor neuron and all the fibers it innervates - Smallest amount of muscle can be activated voluntarily - Recruitment of motor units is the most important means of controlling muscle tension - Once recruited, all fibres within a motor unit contract simultaneously - Alpha 2 motor neurons innervate type 1 fibres - Alpha 1 motor neurons innervates type 2 fibres Motor neurons - Motor I contracts then IIA and then IIX. - Firing rate for I is low - Firing rate for IIa is medium - Firing rate for IIX is high Mammalian skeletal muscle fibre types - Type of motor neuron and the recruitment pattern dictates the myosin isoform expressed in every fibre of the particular motor unit Slow twitch MHC I: TYPE I FIBER Fast twitch MAC IIA: TYPE IIA MHC IIX: TYPE IIX MHC IIB:TYPE IIB - Myosin heavy chain isoform determines myosin-ATPase activity - Myosin atpase is directly related to max shortening velocity - Humans do not express MHC IIB - MHC IIB > MHC IIX > MHC IIA Human skeletal muscle fibers - Fibre metabolic characteristic have several enzymes whose activity is measured to quantify metabolic Characteristics: - Glycolytic capacity - Oxidative capacity Rank from least to greatest GPDH: I is low, IIA is medium and IIX has the greatest GPDH rate Mitochondrial density: IIX has the lowest density, IIA has medium and I has the largest density SDH: IIX has the lowest, IIA has the medium and I has the greatest SDH. Skeletal muscle fiber – morphological characteristic - Muscle fiber diameter (Size) - Capillary density (muscle blood flow) - Myoglobin contact (cellular o2 storage and transport) Myoglobin concentration - Highest concentration = I - 2nd highest = IIA - 3rd Highest = IIX - Lowest = IIB Summary - Motor units that stimulate fast fibers, tend to innervate larger amount of muscle fibers and that is why they produce more force - Assuming a single muscle fibre is maximally stimulated what determines how much force it will generate? Cross sectional area! - Large fiber = more myofibrils it contains - More myofibrils = more sarcomeres = more crossbridge and therefore more force What will determine fatigue resistance of fibre? Fatigue resistance is directly related to fibre mitochondrial contact/volume. Isometric static: contraction where the overall length of muscle does not change and the joint angle does not change Isotonic: performed at constant tension or levels of production Isokinetic: contraction and constant velocity Concentric: muscle produces a force that exceed the load (demand) and the overall length of the muscle shortens and joint angle gets smaller Eccentric: muscle is producing force that does exceed the load as a result the overall length of muscle lengthens and joint angle get longer Power: amount of work performed per unit time. Force x shortening velocity Twitch: a brief contract and relaxation of skeletal muscle caused by a single electrical stimulus Latent period: delay from the stimulus to the onset of force production Pt- peak tension, the highest force measured during a twitch CT – the time from onset of force production to pt Single twitches: muscle relaxes completely between stimuli Summation - stimuli closer together and does not allow muscle to fully relax - summation of force leads to unfused tension - stimuli are far enough apart to allow muscle to relax slightly - summation leading to complete tension > muscle reaches steady tension Bioenergetic and metabolism Metabolism: the total of all cellular reactions including all those concerned with synthesis of molecules and breakdown of molecules Bioenergetics: the process of converting the energy stored in chemical bonds in things like glucose or fatty acids into high energy bonds in molecules that can be used to do work ATP - phosphate bonds are high energy bonds - energy from food substrate molecules is converted into phosphate bond energy in atp - atp phosphate bond energy is released in thousands of different reactions to provide energy for processes including synthesis, transport, work, heat - a constant supply of atp is essential for the cell in order to match energy supply with energy demand - rate of energy demand increases in proportion to exercise intensity and that energy must be provided for the duration of exercise - during intense contractions, skeletal muscle atp utilization rate can increase by as much as 100 x when compared to rest - energy supply pathway must be responsive to signals associated with changing energy demand in order to provide the necessary bioenergetic response atp supply reactions - high energy phosphate buffering systems and metabolic pathways to convert energy from metabolic substrates into atp - atp is stored in limited amounts in skeletal muscle - the rate of atp demand has to be precisely met by atp supply reactions even when demand for atp increases - homeostasis is compromised and contractile function is impaired when atp isn’t meant causing fatigue anaerobic - does not require oxygen - high energy phosphate transfer: primarily stored in ATP and PCr. - Anerobic glycolysis Aerobic - Requires oxygen - Oxidative phosphorylation: metabolic pathways used to harness energy from carbs,fats and amino acids to produce atp - Oxygen is required in electron transport chain and acts as a final electron acceptor HEPT system - Important at onset of exercise, during transition to higher intensities or heavy exercises Atp + H2O ---- ADP + Pi + high energy - Only atpase  - Stored atp – only enough atp - Stored in skeletal muscle to sustain 2-3 seconds of heavy exercise - Atp is available for immediate use by ATPase ADP + PCr + H ------- ATP + Cr - Creatin kinase - Creatine kinase is very high in muscle to replenish ATP rapidly as ATP is hydrolyzed during exercise - Near equilibrium reaction and all you need is a small decrease in atp to shift reaction to the right - When you stop working out ATP increases and moves equation to the left ADP + ADP ------ATP + AMP - Adenylate kinase - Fav reaction because keeps adp low and reduces kcal - Reversible reaction : increases atp when the rate of atp hydrolysis is high - Keeps adp low which maintains amount of energy released from atp hydrolysis AMP ----- IMP + NH3 - Amp deamnase - Reaction keeps amp low which keeps reactions #3 moving to the right Glycolysis - Occurs in cytosol - Anaerobic process - Utilizes glucose from the blood and from glycogen (stored in liver and skeletal muscles) - CHO storage is greater than ATP and PCr storage, thus we can rely on glycolysis for ATP production for longer periods of time - The rate of atp production is slightly slower relative to the Hept system Net yield Blood glucose + 2 ADP + 2Pi -------- 2 lactate + 2H + 2 ATP Or Glycogen + 3 ADP + 3Pi ------ 2 lactate + 2 H + 3ATP - Glycogen is the primary source of CHO in skeletal muscle Glycogen: insoluble, it lower osmotic pressure by reducing free glucose concentration Glycogen synthesis: adds glycose units to glycogen. Aka produces glycogen - Hexokinase requires atp for energy if using blood glucose - PFK uses atp for reaction: ATP to ADP 3 stages of oxidative metabolism  1. Formation of acetyl co-a from pyruvate or fatty acids 2. Energy in the form of electrons and the accompanying H is harnessed by NADH and NADH2. 3. NADH2 AND FADH2 donate electrons and H+ to the electron transport chain. Energy from the electrochemical gradient drives atp formation from ADP + Pi Heat, energy expenditure and calorimetry - To sustain all body functions there is a constant expenditure (usage) of atp - Production of atp requires consumption of foodstuff and oxygen - Process results in the release of heat energy - The rate of heat production is directly proportional to energy expenditure and metabolic rate Direct calorimetry: accurately quantifies energy expenditure by measuring heat released by an individual Indirect calorimetry: estimates energy expenditure by measuring chemical by products of metabolism (oxygen consumption and carbon dioxide production) - Since there is a direct relationship between oxygen consumption and the amount of heat produced by the body, the measurement of oxygen consumption provides an indirect but accurate estimate of whole body energy expenditure Vo2 whole body consumption - Oxygen uptake - The volume of oxygen that the whole body utilizes to produce atp in a given period of time - Expressed in absolute terms L/min or mL/min - Relative mL/kg/min - Vo2 is a function of the bodys ability to take up oxygen from the atmosphere, deliver it throughout the whole body to use it to produce ATP. - 70kg male rest VO2 = 0.25 L/min or 3.5 mL/Kg/min VCO2 whole body consumtion - Volume ofcarbon dioxide that is produced by the body - Absolute or relative - Metabolic production: krebs cycle, tricarboxylic acid, citric acid - Non metabolic: buffering of H via bicarbonate - Male rest = 0.20L/min or 2.8 mL/kg/min The respiratory exchange ratio, respiratory quotient and substrate utilization Respiratory quotient: RQ reflects the composition of fuels oxidized at rest and during exercise in the cells body Respiratory exchange ratio: measure at the mouth and thus is an estimate of RQ. Mostly accurate, however at the onset of exercise, during heavy intense exercise or post-exercise the accuracy of RER estimating RQ is reduced. RER: VCO2/VO2 Glucose oxidative metabolism summary equation: C6H12O6 + 6O2 ---- 6CO2 + H2O Palmitate oxidative metabolism summary equation: C16H32+ 32 O2------16CO2 + H2O CHO oxidative - 4.1 kcal/g - 5.05 kcal/ L O2 - 1.0 RER Fat oxidative - 9.1 Kcal/g - 4.70 kcal/ LO2 - 0.7 RER The fick equation and determinants of VO2 VO2 = CO x (CaO2 – CvO2) Vo2: volume of oxygen consumption/utilization CO: cardiac output (L blood/min) CaO2: content of O2 in arterial blood (mL of O2/L blood) CvO2: content of O2 in venus (mL/O2/Lblood) CO= HR x SV Therefore VO2 = HR x SV x (cao2-cvo2) SV = volume of blood ejected from ventricle during each heart beat Rest to exercise - There is an instantaneous increase in atp demand that is directly proportional to exercise intensity Can our muscles provide immediate supply of atp needed to perform this task? Yes, by creatine phosphorylation, stored atp, oxidative phosphorylation, hept, and anaerobic glycolysis. VO2 kinetics and oxygen deficit Vo2 kinetics: the exponential increase in VO2 from a prior value (rest or lower work rate) to a new steady state Oxygen deficit: the difference between measured VO2 and the steady-state value after the onset of exercise Margaria: “serial mobilization theory”  1. PCr immediate and only substrate for atp resynthesize in first 10 seconds 2. When PCr depleted, glycolysis is activated to provide a continued ATP supply - THIS IS NOT TRUE. - Glycolysis rate in increase (activated) immediately at the onset of exercise and blood flow increases and enzymes involved in oxidative phosphorylation are activated. - All atp supply pathways are always active - The relative contribution of each pathway can change with time and exercise intensity VO2 required: 3.0 L/min Energy required: 3.0L/min x 5kcal/min At time 0 - Vo2 = 0.25L/min - 0.25/3 = 8% - Therefore, 92% of atp is coming from anaerobic sources At time 1 min - Vo2=1.9 L/min - 1.9/3 = 63% - Therefore, 37% of atp is anaerobic At time 2 min - Vo2=2.6L/min - 2.6/3 = 87% - Therefore 13% of atp is anaerobic O2 deficit and EPOC - O2 deficit and “steady state” are influenced by exercise intensity - VO2 plateaus in 3min vs 4 min EPOC: excess post exercise oxygen consumption - Elevated VO2 for several minutes immediate following exercise Rapid components of EPOC - Resynthesize of PCr overall: ADP + PCr --- ATP + Cr - Replacing muscle (myoglobin) and blood O2 stores Slow component of EPOC - Elevated body temp and catecholemines - Conversion of lactate to glucose - Elevated HR and ventilation above resting values Kinetics at onset of exercise - Rapid increase in HR,SV, CO at onset of exercise (within 1 sec) - Takes approximately 1-4min until steady state HR,SV,CO at constant workload - Rapid decrease in HR, SV, CO during recovery after exercise Blood flow kinetics Hemodynamic responses to heavy cycling Submaximal steady-state exercise - Light exercise why? - Assume someone has resting RER of 0.8. what will happen to RER at onset of exercise and once steady state is achieved? Why? - Exercise will increase RER (just as an example from 0.8 to 0.9) which indicates a shift from FFA oxidation to CHO oxidation - Increase RER is dependent on exercise intensity - 0.80 – 0.87, the magnitude of the response is dependent on exercise intensity Progressive exercise test – incremental test – graded test - Protocols that posses a systematic and linear increase in exercise intensity of a defined period of time until the individual is unable to maintain or tolerate the work load - Step model vs ramp model How to determine VO2 max (progressive exercise test) Physiologically: maximum ability of the respiratory and cardiovascular systems to take up O2 from the atmosphere, deliver the O2 to the muscles (and other tissues/organs) and for the mitochondria to utilize the O2 to produce ATP. Graphically: VO2 max occurs when there is a leveling off or plateau in VO2 despite an increase in workload Plateau is important: an increase in VO2 = 1.15. due to buffering of acid = higher RER 3. Achieving HR mac: 220 – age or 208 – (0.7 x age) 4. RPE >= 17 (using borgs 6-20scale). VO2 max peak values on treadmill can be greater than bike - Vo2 man observed on a treadmill can be 20% greater than observe on cycle What contributes to greater vo2 when running? - Larger active skeletal muscle mass  - Higher cardiac output - Larger (a-v) O2 - Greater vascular conductance Force production during progressive exercise - During gxt the wort rate goes up every 2 minutes - In order to push pedals and maintain cadence (rpm) your muscles must generate more force - As exercise intensity increases, we must recruit more motor unit: I >IIA >IIX - All type I fibres fire and continue to generate force - Generate more force on pedals and will either collect more action potentials and ATP or recruit skeletal muscles Substrate utilization during exercise: crossover concept - As exercise intensity increases there is an increase in CHO oxidation and decrease in FFA oxidation - Recruitment of type II fibres (fewer mitochondria, more glycolytic enzymes to type I) - Increased EPI in blood stimulates phosphorylase and increase glycolytic rate = increase in lactic acid production - Increased (la and H) in blood, H inhibits lipases, which reduces the rate of lipolysis = reduce FFA delivery to skeletal muscle - Reduced blood flow to adipose tissues Blood lactate response to progressive exercise Lactate threshold: the work rate where blood lactate begins to increase exponentially Onset of blood lactate accumulation: the work rate where blood lactate equals 4 mM What determines the concentration of lactate in blood? Rate of appearance - Recruitment of type II fibers (better suited to produce atp anaerobically) - Increase epi = increase phosphorylase activity = increase glycolytic rate = increase lactic acid production - Increase during GXT Rate of disappearance  - Removal of lactate from the blood by other tissues Relationship between VO2, VCO2, RER, blood lactate and Ve - Increase in active muscle fibres = increase rate of CO2 production - At some point VCO2 = VO2 - At very heavy Work rate, VCO2 > VO2, why? Metabolic CO2 and H buffering in blood from lactive acid - CO2 and H are potent stimulators of ventilation: Ve will increase disproportionately at high work rates. - Note linear at low moderate work rates to match ventilation to metabolic demand - RER reflects the shift in substrate utilization where the point VO2=VCO2 is when RRER = 1.0 and 100% of energy used to produce atp is provided by glycose Metabolic response to progressive exercise Tissue metabolites: during exercise, metabolites are produced in skeletal muscle cells. Some metabolites diffuse or are extruded (transported) out of the cell and the concentration of these metabolites increases in the interstitial fluid - The concentration of metabolites in the ISF is proportional to metabolic rate - The vasodilatory effect is proportional to the concentration of metabolites in the ISF  - Allows tissues to coupe and metabolites to blood flow HR response to progressive exercise? - At onset of exercise and at low to moderate workloads the primary factor responsible for the rise in HR is withdrawal of PNS stimulation - From 100bpm onwards the primary factor that increases HR is the release of NE from SNS nerves that innervate the SA node - Linear response for heart rate response - PNS withdrawal rest HR to intrinsic HR Control of HR – resting membrane potential - Electrical potential across the cell membrane - In a resting cardiac myocyte, Em is -90mV Determined by: - The concentration of positively (cation) and negatively (anion) charger ions across the cell membrane - The relative permeability of the cell membrane to these ions - The ion pumps that transport ion across the cell membrane - The presence of impermeable, negatively charged proteins within the cells that affect the passive distribution of cations and anions - The electrical event that occurs when the membrane potential suddenly depolarizes (becomes negative/more positive) and then repolarize back to its resting state - Initiated by changes in permeability and movement of ions across the cell membrane through specific ion channel 2 types of action potentials in cardiac monocytes: Non-pacemaker action potentials - Typical of most cells in the heart, they are triggered by depolarizing currents from adjacent cells - The connection of the cells through gap junctions allows for this electrical conduction between cells Pacemaker action potential - Occurs in the pacemaker cells of the heart only - Are spontaneously generated action potentials (don’t have to be triggered by external stimuli) - Primary pacemaker cell concentration and actively is in the sinoatrial node, but there are also some pacemakers in the atrioventricular node Electrical conduction system of the heart 1. Action potential originate in SA node and travel across the wall of atrium and to the AV node 2. Action potential pass through AV node and along the atrioventricular bundle, which extends from AV node through fibrous skeleton, into the interventricular septum 3. The av bundle divides into the right and left bundle branches and the action potentials descend to the apex of each ventricle along the bundle branches 4. Action potentials are carried by the purkinjie fibres from the bundle branches to the ventricular walls. Automatic nervous system - Intrinsic HR is approx. 100 bpm - 100bpm HR if all influences on the SA node is removed Bradycardia: Low HR at rest (lower than 60-75) Tachycardia: high HR at rest (over 100) + Ve = factors that cause HR increase -Ve = factors that casue HR decrease - the ANS has SNS and PNS divisions: most organs receive dual innervation from both SNS and PNS Antagonistic controls - SNS tends to activate organs (increase HR) - PNS tends to inhibit organs (decrease HR) Tonic activity - Not on/off but activity of the target organs be adjusted to increase or decrease - Ratio of SNS/PNS activity that determines the net activity of the target Where is this balance /ratio co-ordinated for the cardiovascular system? - The cardiovascular control centre - In the medulla oblongata is a control centre for cardio vascular function - This cente integrates a number of sensory signals with cardiovascular set points and balances the SNS/PNS output to cause appropriate responses of effetor organs - Sns accelerates HR, PNS deceleratesHR via influences on the SA node firing rate  - Pns carried in vagus nerve fibres to SA and AV node - Postganglionic PNS fibre use neurotransmitter Ach - Ach acts on muscarinic cholinergic receptor node cell to hyperpolarize SA node cells. Hyperpolarization leads to decrease rate of spontaneous action potentials and therefore decrease HR. - At rest, PNS tone is the predominant factor that reduces HR from its intrinsic value (100bpm) down to normal resting HR of 60-75bpm - Removing PNS tones (withdrawal) is the primary factor that elevates HR from resting HR up to 100bpm (intrinsic rate) SNS – sympathetic nervous system - SNS carried in cardiac accelerator nerves to SA ad AV nodes and conduction system - Postganglionic SNS fibres use neurotransmitter NE - NE binding to adrenergic receptors causes te rate of spontaneous depolarization of SA node cells to increase HR - Increase in SNS tone is the predominant factor that elevates HR from 100 bpm up to HRmax - Decrease in SNS tone is the predominant factor that reduces HR from high rates down to 100bpm - SNS also innervates the cardiac myocytes to affect the strength of their contraction Regulation of stroke volume - SV = EDV – ESV - End diastolic volume: end of diastole, volume of blood in left ventricle (120mL). this is when the ventricles is at its fullest and just before contraction - End systolic: end of systolic, volume of blood in the left ventricle after contraction/ejection (40mL) - End of systolic, volume of blood leftover Preload: the stretch of the ventricle at the end of diastole. EDV is a main determinant of preload  - Increase in EDV = increase in preload = increase in SV Afterload: the force/pressure that the ventricle must overcome to cause ejection of blood during systole. Aortic pressure or MAP is a main determinant of afterload - Increase in Afterload = increase in ESV = decrease in SV Inotropy/contractility: the strength of the ventricular contraction during systole. Determined by cellular mechanism controlling the -contraction coupling process in ventricular myocytes. SNS/PNS activity is a regulator of contractility. - Increase in contractility (increase in PNS/SNS) = decrease in ESV = increase in SV How does preload affect SV? Length-dependent activation of the heart: heart must pump all of the blood that is returned to it (venous return). Therefore, increasing venous return and thus, ventricular preload, must lead to an increase in SV. Venous return: the volume of blood returned to the heart by the veins each cardiac cycle and is a major determinant of EDV - Mechanisms work in opposite way to accommodate decrease in VR. Thus decreasing VR and ventricular preload must lead to an decrease in SV. - Filling the ventricle = length dependent activation - Fill it, alls will expand and stretch which means the sarcomere lengths get longer and heart has a contraction - All the blood that returns to the heart needs to be ejected Factors regulating venous return 1. Venoconstriction - Relating to veins - Specialized functions of veins is that they are capacitance vessels - They are well adapted to contain a lot of volume - Walls are compliant and the level of basal tone in the venous smooth musle is low 2. Skeletal muscle pump - Mechanical factor  - Vasoconstriction does happen during exercise - The skeletal muscle pump is strictly a mechanical with skeletal muscle contraction of relaxation and contraction - Venous valves are one-way - Blood from tissue capillaries and venules drains into the veins - When skeletal muscle contract it compresses the veins and forces the blood to move towards the heart - When skeletal muscle relaxes the compression is removed, blood draining from the tissue vasculature refills the veins - Thus during rhythmic, dynamic exercise (repeated contraction/relaxation), the skeletal muscle pump enhances VR, while during isometric contractions the muscle pump does not function and VR is reduced 3. Respiratory pump - Mechanical factor - Increase in VR during exercise - Inspiration lowers the thoracic pressure and elevated abdominal pressure - The compartment pressure gradient during inspiration helps pump venous blood from the abdomen into the thorax to increase VR - The effect is present but is greatly enhanced during dynamic exercise, as respiratory rate and depth of breathing are both increased in proportion to exercise intensity How does afterload affect SV? - Aortic or map is a barrier to the ejection of blood from the left ventricle-sufficient pressure must be generated In the ventricle to overcome the map and cause ejection - SV is inversely proportional to afterload - Changes in afterload shift the SV vs EDV curve up or down - Degree of curve shift scales with degree of afterload change - During dynamic exercise, large declines in peripheral resistance due to arteriolar dilation in skeletal muscle prevent large increase in MAP and afterload from occurring - Makes is possible for the heart pump the cardiac output necessary to support the O2 demands of the body How does inotropy/contractility affect SV? - Cardiac monocytes contain numerous calcium regulatory proteins, and the numerous regulatory sites on contractile proteins that control the force generated during contraction - All sites of inotropy control - Many of these proteins are sites that are regulated b cell signaling mechanisms under the control of the beta-adrenergic receptor system - Via this mechanisms, SNS activation and or circulation epinepherine and norepinepehrine causes increase in contractility - Therefore, calcium can control amount of force Summary of effect of muscle pumps - LV filling is enhanced during progressive exercise by the muscle pump, respiratory pump and venoconstriction. Despite a progressive reduction in the time spend in diastole - As HR increases, cardiac cycle duration decreases. - SV regulation: afterload increases during progressive exercise. Pressure of LV must generate to eject blood increases. - Ejection fraction increases despite increased afterload What drives the increase in VO2? - Cardiac output response to progressive exercise and CO redistribution during exercise - Blood flow to active skeletal muscle is increased in proportion to exercise intensity and attempts to match the demand ofr oxygen and substrates and attempts to match removal of waste products to waste productions Blood pressure response Normal ranges: SBP: 120 mmHg DBP: 80 mmHg MAP: 90 mmHg - SBP increases the most 120 to 200mmHg - Map may increase 20-30% during maximal during dynamic exercise - DBP will increase slightly 5-10mmHh during a progressive exercise test on a bike. It could also remain the same or decrease slightly. - Treadmill will usually cause a drop in DBP Ventilation and gas transport in the blood - CaO2: arterial O2 content is determined by ventilation, respiration, hemoglobin concentration and Hb saturation - CvO2: dependent on metabolic rate of the tissues and blood flow to tissue Pulmonary structure and function Conducting zone - Trachea and bronchi are rigid tubes (cartilage) - Bronchioles are soft, dynamic tube (smooth muscle-dilates during ex because of SNS stimulation – decrease resistance to air flow) - 4 primary functions: conveys air to alveoli, warms air, humidifies air and filters are Trachea, bronchi, bronchioles, terminal bronchioles Respiratory zone - Respiratory bronchioles have sporadic alveoli - Alveoli is site of gas exchange Respiratory bronchioles, alveolar ducts, alveolar sacs Uptake of O2 from the air in the lungs by the pulmonary capillary blood Changes in PO2 throughout the pulmonary and systemic circulation - As blood flows through systematic capillaries, PO2 in the blood equilibrates (diffusion) with the tissue PO2 PTO2 is a function of 1. O2 delivery to the tissue (blood flow) 2. O2 utilization (mitochondrial O2 consumption in the tissue) Components of blood Plasma: (58%) liquid portion of the blood. Contains ion, proteins, glucose, fatty acids, water, hormones and nutrients. 2-3% of the O2 carried in the blood is dissolved in the plasma Hematocrit: is the % of the total blood volume that is occupies by RBC normally. 42% in males and 38% in females Hemoglobin content of healthy blood: - Males: 15 g Hb/ 100mL blood (150 g Hb/L blood) - Females: 12.5 g Hb/100mLblood (125 g Hb/L blood) Hemoglobin content of diseased (anemic) blood: - Females and males: 8-11 g Hb/ 100mL blood - 97-98% of the o2 in the blood is carried bound to Hb in RBC - Buffy coat(100 million Hb molecules in 1 red blood cell and there are trillions in your body - Normal SO2 is 96-98% at rest in arterial blood What is oxygen carrying capacity of the blood? O2 carrying capacity of the blood: the maximum volume of O2 that a volume of blood can carry at full saturation - since saturation is 100%, carrying capacity depends on Hb: 15g Hb/100mL blood males 12.5g Hb/100 mL blood females - each Hb molecules can bind a maximum of 4 O2 molecules - a full saturation of Hb with O2 this amounts to 1.34 mL O2/g Hb - so maximal O2 carrying capacity of the blood 15g Hb/100 mL x 1.34 mL O2/g Hb = 20 mL O2/100mL blood - if Hb changes, the O2 carrying capacity of the blood will change what is the oxygen content of blood? O2 content of the blood: the volume of O2 carried in each volume of blood under given conditions - CaO2 depends on carrying capacity (Hb); Po2 that the blood is exposed to and thus, SO2 - O2 content = carrying capacity * saturation - CaO2 = 20 mL O2/100mL blood x 0.97 = 19.5 mL/100mL blood - CvO2= 20 mL / 100 mL blood x 0.72 = 14.5 mL O2/100 mL blood - Arterial oxygen content assume that partial pressure of oxygen in arterial blood is 100 mmHg which results in a SO2 of approximately 97%  - Venous oxygen content assume that the partial pressure of oxygen in venous blood is 40 mmHg at rest, which results in a SO2 of approx 72% O2 hemoglobin dissociation curve Changes in arterial and venous PO2 and during progressive exercise - During progressive exercise the rate of O2 consumption increases - As a result muscle oxygenation or the Po2 in the active skeletal muscle cells decreases - Mitochondria are consuming large amount of O2 - More O2 dissociates from Hb and diffuses into the muscle cells thus the PO2 of the venous blood is decreased Co2 transport and pH buffering in the blood 1. Co2 can bind to Hb 2. CO2 can dissolve in plasma 3. Co2 can be converted to bicarbonate via the reaction below Wingate test - Requires 30 seconds of “all-out” effort - WR is relative to body mass – on cycle ergometer the resistance is applied by weights - Weight is equal to body weight (x 0.075) What information can we derive from the test - Peak power - Mean power - Fatigue index - Anaerobic capacity Power output is typically calculated every 5 seconds of the test Total of 6 PO’s - 54kg female; test weight = 54 x 0.0075 = 4kg - Highest rpm was 105 rpm Equation 1: PO= tension (kg) * distance (m) / time (s) Equation 2: distance = rpm * distance per revolution (m) Combine PO = tension (kg) * rpm * stance per revolution (m) / time (s) PO = 4 * 105 * 6/5 PO = 504 W Absolute power output Relative power: 504 W/54 kg = 9.33 W/Kg Fatigue index = (peak power – lowest power) / peak power *100 Energy demand during wingate test  - During submaximally steady state exercise the power output is constant because the resistance / tension and rpm/cadence are not changing - Since the wingate test is performed on a cycle ergometer with a fly wheel, the power output is directly related to pedal rpm – thus as you slow down the power putput decreases - 8 males; 20 years; 80kg. VO2 peak = 3.66 L/min WRmax = 223 W - Convert W to Kg-m/min: 1100 W = 6600 kg-m/min - VO2 = WR x 2 + 300 = 6600 x 2 + 300 = 13.5 L/min - Energy required = 13.5 L/min * 5Kcal/LO2 - Energy required = 67.5 kcal/min (if the power output could be maintained but cant) - Time 0.125 / 3.5 x 100 = 9.3% aerobic. Therefore 90.7% anaerobic Hemodynamic response to the Wingate test and post-exercise hypotension - Like the HR, SV and CO response – the blood pressure response to a wingate is similar in magnitude to a progressive exercise test What is post-exercise hypotension? - Transient (temporary) decline in BP following exercise (aerobic, resistace, anaerobic) Who will experience post-exercise hypotension? - Not everyone, most common in people with hypertension. Magnitude of BP declines in greatest in people with hypertension What causes post-exercise hyotension? - Primary due to reduced vascular resistance-cause of vasodilation could be metabolic, neural and/or hormonal in nature Physiological response to resistance exercise - Can be more varied compared to aerobic exercise or the Wingate. With resistance exercise you need to consider multiple factors Factors: - Muscle mass involved - Intensity is 1% RM - Format (circuit vs consecutive)  - Temp: velocity of exercise - Rest between sets - Number of sets and repetitions How long does a typical set last? - 10-15 seconds Which pathway is most important for ATP production during the resistance exercise activity? - Anaerobic sources: stored atp,hept, glycolysis Which pathway is most important during the test period (between sets)? - VO2 oxidative phosphorylation Energy demand and VO2 response during resistance exercise Hemodynamic response to intense resistance exercise - A valsalva maneuver is a forceful exhalation against a closed glottis - Often performed when lifting heavy objects and is instinctive during high-intensity resistance exercise or submaximal resistance exercise performed to muscular fatigue - Valsalva maneuver contributes to the increase in arterial BP by actively compressing the heart and blood vessels in chest and abdomen (due to increased thoracic pressure) - In addition, > 30% MVC will cause total occlusion of microvascular due to skeletal muscles compressing the microvasculature Mechanical effects of muscle contraction on the pattern of skeletal muscle blood flow during dynamic exercise 3 steady important phases: - Steady: blood flow at rest - Phasic: blood flow during exercise - Steady: flow during recovery Rest: blood flow is low why? Metabolic rate (O2/ATP demand is low. BF is steady / smooth because there is no skeletal muscle contraction Exercise: BF is phasic due to pattern of skeletal muscle contraction an relaxation. Average BF increase in proportion to metabolic demand (in proportion to exercise intensity) Recovery: Metabolites remain elevated in ISF. The concentration will slowly decrease and with it BF will decrease. BF is steady/smooth because there are no more skeletal muscle contractions The pattern of skeletal muscle blood flow before, during and after isometric contractions of varing intensities? Rest: both 5% and 50% MVC – BF is low why? Metabolic rate (O2 ATP demand) is low. BF is steady/smooth because there is no skeletal muscle contraction Exercise: - 5% MVC – BF is steady/smooth because there is only 1 sustained contraction (30 minutes). Average BF increase in proportion to metabolic demand (in proportion to exercise intensity) - 50% MVC – BF is steady/smooth because there is 1 sustained contraction (1.5 minutes). Average BF does not change substantially from rest! Recovery: - 5% MVC – metabolites remain elevated in ISF. The concentration will slowly decrease and with it BF will decrease. BF is steady/smooth because there are no more skeletal muscle contractions - 50% MVC – metabolites accumulated (were trapped in the ISF) since blood flow did not increase during exercise. Large increase in BF during recovery to remove metabolites, restore O2 stores, resynthesizes PCr and ATP, metabolizes lactate Blood pressure response to isometric exercise - During isometric static contraction TPR increases despite there being metabolic induced vasodilation in the active skeletal muscle vascular networks - This is because skeletal muscle contractions compress the microcirculation even at low intensity, with complete occlusion at >30% MVC. Adaption to endurance - Frequency - Intensity - Time - Type - Volume - Progression Changes in VO2 max following endurance training What happens to VO2 max following endurance training?  - VO2 = HR x SV x (CaO2 – CvO2) - If the vo2 max is increased then any or all of the variables above could be increased Why is VO2 the same at 100W pre-training vs post-training? - 100 W is the same absolute work rate: in theory there is the exact same ATP demand - Assume mechanical efficiency does not change, therefore VO2 required at a given absolute WR does not change Limitations to Vo2 max What determines magnitude of adaption? 1. Genetics 2. Initial training status - We all have physiological ceiling whereby increasing training volume does not lead to further adaption - Heart can only hypertrophy so much - Relative changes in VO2 max varies wildly. - Heritage subjects were recruited, tested post exercise-trained program for 20 week and average increase in Vo2 max was 19% Effects of endurance training How do the cardiovascular and metabolic response to onset of exercise and steady state exercise change following endurance training? - Cycling at same absolute work rate before and after endurance training - Faster vo2 kinetics - Smaller o2 deficits Vascular adaptations: - Increase # of capillaries and # of capillaries in parallel - Enhanced vasodilation of arterioles - These will decrease to a greater extent and thus increase BF Cardiac adaptations to aerobic training What is the adaptation? 1. LV dilation which increase ventricular chamber size (fillable volume) 2. Compliance of the heart wall increase (stretches easier) 3. Cardiac hypertrophy = increase ventricular wall thickness and pump strength which promotes and decrease in ESV and therefore increases SV - Increase and EDV and therefore increase in stroke volume - Increased in sarcomeres per cardiomyocyte not an increase in the number of cardiomyocytes - Aerobic training induced cardiomyocyte hypertrophy can mean more sarcomere in series and or more sarcomeres in parallel (increased myocyte width) - More sarcomeres = more crossbridge = more force What is the stimulus that triggered the adaptation? - Stretch (preload) – eccentric hypertrophy - Afterload – concentric hypertrophy - Neurohumoral - Metabolic many intracellular pathway Adaption to blood Would CaO2 change? - It is possible but might require someactivities that violate anti-doping rules - CaO2 – CvO2 does not change How does a change in total blood volume affect Vo2 max? - Increase blood volume = enhanced VR = increased EDV = increased preload = increased SV What adaptations occur in the microvasculature as a result of endurance training? 1. Structural remodeling of muscle microvascular network - A increase in number of capillaries - B increase in number of capillaries in parallel with each other - C increase in tortuosity of capillaries - Increased potential to decrease Rmuscle when there is appropriate vasodilation of arterioles upstream of capillaries 2. Improved control of vasodilation and opening/recruitment of capillary networks - Many cell signaling pathways in endothelial cells and in vascular smooth miscle cells are altered by endurance training in ways that enhance the responsiveness of the arterioles to vasodilatory signals What is the functional effect of angiogenesis – more capillaries? - In response to aerobic training, there is an increase in the maximal skeletal muscle blood flow (increase in the number of capillaries and decrease in resistance to blood flow) - An increase in surface area for diffusional exchange is also facilitated by the increase in capillaries and by increase in the tortuosity of capillaries - An increase tortuosity of capillaries will help prevent very fast transit times of red blood cells. Thus the time for diffusion is maintained. This is very important adaption because maximal (a-v)O2 is not affected by endurance training - Thus, no increase in tortuosity, then faster transit time may create a diffusion limitation and maximal (a-v)O2 would be lower in highly trained people Pulmonary adaptions to endurance exercise? In untrained healthy people does the 5-10mmHg drop in arterial PO2 affect CaO2 much? - Not really, SO2 may drop from 98% to 96% - In elite athlete SO2 may drop to 90% Tight vs loose metabolic control Tight - Trained - Broad range of metabolic and work rates, the concentrations of PCr, Pi, ATP and ADP show very minimal change despite large increases in ATP demand and large increases in ATP supply Loose - Untrained - Concentrations of PCr, Pi, ATP and ADP show large changes when large increase in flux occurs through ATPases and mitochondrial ATP synthesis Untrained athlete vs trained athlete at 150 W - Requires a VO2 of 2L/min - To sustain activity, rate of atp hydrolysis is 100 units/minute and the adp formation is 100 units/minute - Adp must be transported into mitochondria where it is converted to atp - Since number of mitochondrial is double in trained individual the rate of adp transport is double and thus the concentration of adp will be ½ in the trained - Decreased adp = less stimulation of glycolysis = less lactate production - Decrease adp = reduced breakdown of PCr Effects of endurance training on substrate utilization and metabolism at absolute submaximal work loads 1. Increase in fat oxidative 2. Decrease in glycolysis 3. Decrease in CHO utilization 4. Decrease in net glycogen degradation 5. Decrease in PCr hydrolysis 6. Decrease in atp degradation products 7. Decrease in blood lactate accumulation What are mechanism for these training adaptations? - More mitochondria - More triglyceride storage in muscle - Enhanced delivery of ffa to muscle during exercise Sprint interval training compared to classical endurance training Protocol - Untrained men or women - 6 week training protocol: - SIT: 4-6s wingates, 4.5min recovery b/w sets, 3x/week - ET: 40-60min, 65% VO2 peak cycling, 5x/week - Time: 1.5h/week vs 4.5h/wk - Volume: 225kJ/wk vs 2250 kJ/wk  - The compared responses to 1hr 65% VO2peak cycling: pre-post training SIT includes similar metabolic adaptations as endurance training Skeletal muscle adaptations to strength training Agonists – muscles mainly responsible for producing force in the intended direction of movement - Must be fully activated Synergists – muscles that assist in coordinating the movement - Must be appropriately activated Antagonists – muscles that apply force in the opposite direction of agonists - Must be appropriately inactivated Muscle strength – peak force developed during a maximum voluntary effort (depends on muscle length and velocity of contraction) Muscular power – the explosive aspect of strength defined as the rate at which mechanical work is performed - Low speed strength and power (rowing, swimming) - High speed strength and power (sprinting, tackling) - Explosive strength and power (jumping, spiking) Muscular endurance – ability to sustain repeated muscle actions (repitions) or to sustain fixed static muscle actions for an extended period of time (max # of repetitions at a given percentage of 1RM) Increase in force are specific to the joint angle training was performed Increase in muscle power are specific to the shortening velocity during training Fast contractions – training increased vmax. Thus, peak power increased and it occurs at a higher velocity A: pre-training force velocity curve B: post-training force velocity curve C: pre-training power-velocity curve D: post-training power velocity curve Neural and muscular adaptations to strength training - Strength performance is determined not only by the size of the involved muscles but also by the ability of the nervous system to appropriately activate these muscles Strength training increases muscle strength/power by:  1. Neural adaptation 2. Increased muscle size (hypertrophy) Neural adaptation evidence: unilateral training studies - Those who are novice with respect to resistance exercise will see early increases in strength in the absence of measurable hypertrophy (muscle girth or fibre CSA). - Unilateral resistance training: strength increases in both the trained and untrained limb - Trained due to neural adaptions and hypertrophy - Untrained due to only to neural adaptations Emg studies: increased quantity of recorded EMG generally indicates that more motor units are recruited, motor units are firing at hiring rates, or some combination has occurred Neural adaptation to resistance training 1. Increased activation of agonist - Some “high-threshold” motor units are only recruited during an MVC and untrained people may not be able to recruit these motor units - The average motor unit fires at a frequency of 10-60Hz and therefore possible to increase firing rates of motor units with strength training 2. Reduced antagonist coactivation - Any co-activation of antagonists will reduce force output of the agonist - Resistance training reduces antagonists coactivation 3. Increase rate of force development (ballistic movement) - Associated with several factors (eg. Neural, excitation-contraction coupling) 4. Synchronization of agonists within a muscle group Resistance training-induced muscle hypertrophy - Muscle size primarily determined by fibre size but also affected by genetically determined # of fibres - Strength training does not affect number of muscle fibers (hyperplasia-number) - Strength training increases muscle fibre cross sectional area - Increase in cross-sectional area associated with large increase in myofibrillar content in muscle cells (actin and myosin) - Increase in myofibril are means there are more sarcomere in the muscle cell - Max force production directly related to cross sectional area What is the stimuli created during resistance exercise that causes hypertrophy - Acute resistance exercise creates several stimuli (force, strength, damage, inflammation, metabolic stress, neuroendocrine, hormonal)  - Hormonal mechanisms help mediate both short-term homeostatic control and long-term cellular adaptations to resistance exercise and training. Anabolic hormones associated with muscle hypertrophy: - Growth hormone - Insulin-like growth factor - Testosterone Early phase of hypertrophy is due to increased muscle protein synthesis - The rate of muscle protein synthesis and muscle protein breakdown are constantly changing - Over hour and days these two rates are equal and muscle mass is maintained Hypertrophy is due to an increase in the number of myonuclei and an increase in translational capacity 1. Ribosomal transitional capacity can increase = produce more protein 2. Satellite cells can become myonuceli. More nuclei means more translational machinery which means transition of more protein Mitochondrial and capillary adaptations to resistance training - Mitochondrial volume is relatively unchanged following resistance training. Is the absolute volume of mitochondrial larger? Yes relative no - Capillary density (# of capillaries per cross-sectional area of muscle) is relatively unchanged following resistance training. Is the absolute number of capillaries larger? Yes Class 8 Fatigue - Reversible decline of muscle performance during activity - Muscles get weaker and slower: reduction in the force, shortening velocity, relaxation and/ or power that a muscle or group of muscles can generate following exercise (contractions) - Most recovery occurs within the first hour - There is a slow reversible component that can take several days to reverse Injury - Common with eccentric contractions - Decline in muscle performance that reverses very slowly - Characterized by sarcomeric disorder, membrane damage and inflammation - Recovery may involve activation of satellite cells and regeneration of damaged fibres - Muscle damage is when Z disc isn’t straight Typical experimental steps used to assess fatigue - Human transcutaneous electrical stimulation - Isometric contractions - Locked in place and maximal contractions to determine isometric force and moment - Electrode on skin and stimulation muscle to contract (voluntary vs involuntary can be assessed) must have pre and post exercise measurement - Skin fiber technique: pass electro current through bath, one muscle cell and peel sarcolemma off and left with mitochondria Schematic diagram of a mechanically skinned muscle fibre - With this experimental preparation – you control what is in the cytosol, the bathing liquid. You can change the concentration of 1 metabolite at a time and observe the effect it has on force. - In experiment, researcher increases the concentric of Pi Change I contractile properties associated with fatigue - Peak tension decrease - Decrease in +dF/dt and -dF/dt - Increase in CT Factors associated with fatigue/exhaustion - The until the intended force or power output no longer can be maintained depends on the interaction between the required force, the maximum force that the muscles can produce, and the endurance of the muscle cell - Time to exhaustion = total time elapsed from when exercise began to when the individual became exhausted - Solid line indicates the submaximal force or power required to complete a particular activity - Dashed line shows the maximum force declines during repeated stimulation. Performing repeated MVCS over time. Force will eventually drop - Exhaustion occurs when two curves intersect How can model change 1. Decrease in required force will delay the onset of exhaustion. An increase in required force will cause exhaustion to occur sooner 2. Increases and decreases in maximum force that the muscle can produce will also change the time to exhaustion 3. Changes in the intrinsic fatiguability of the muscle will also change the time to exhaustion Level one mechanism: - Where does the failure occur with respect to excitation-contraction coupling and relaxation process that ultimately causes the decline in muscle performance? - For example, ca release Level two: - What causes the impairment or failure of e-c coupling process? What was the mechanism associated with level one mechanism? - Level 2 are either metabolic or non metabolic - Metabolic can be reduced energy supply (atp,pcr,glycogen) and or accumulation of metabolic by products (Pi,Mg,adp, H) - Non metabolic structural damage (eccentric exercise), free radicals (reactive oxygen/nitrogen species), activation of proteolytic enzymes Fatigue and anerobic metabolism - Fatigue develops rapidly when exercise/task/activity/stimulation protocol requires ATP production that exceed aerobic capacity of the muscle fibres (ie, atp demand > aerobic atp supply) aka wingate - Experiments on single muscle fibers have revealed three components underlying the force decrease during this type of acute fatigue: 1. Decreased ability of the actomyosin crossbridge to generate force (decrease in maximal Ca activated force) 2. Reduced myofibrillar Ca2 sensitivity 3. Decreased SR Ca2 release - The first the components relate to impaired myofibrillar function and occur during early fatiguing stimulation - The third component, decreased SR Ca 2 release, generally becomes important in later stages of fatigue Fatigue is normaly associated with reduced activating ca levels Reduced ca sensitivity of the contractile apparatus and reduced maximal ca activated force Incorrect: lactic acid is a major cause of fatigue in skeletal muscle Maybe it’s the hydrogen ion in lactic? Acidosis does not affect maximal tetanic force production, but may impair the rate of relaxation - Acidosis does not affect maximal tetanic force during the first or last contraction  - The number of tetanic contractions require to induce fatigue is not affected by acidosis (amount of exercise needed to cause fatigue) - Rate of relaxation is reduced (slower) during acidosis. Why is this bad? - Recall: tetanus is a maximal contraction induced by electrical stimulation Increased cystolic pi decrease SR Ca2 release Low atp and elevated mg reduce Ca release in rat skinned skeletal muscle fibres - Majority of mg in skeletal muscle cell is bound to adp - High rate of atp hydrolysis (during heavy exercise) will result in an increase in free mg (floating in cytosol) - Mg is a very potent inhibitor of Ryr - Atp will very rarely get as low as 0.5mM Incubation in high Ca abolishes depolarization induced ca release - Recall there is a physical link between DHPR and Ryr  - Depolarization causes DHPR to change shape which results in RyR to open - Ca2 at high concentrations or low from long periods of time can activate proteolytic enzymes - Proteolytic enzymes are proteins that degrade (breakdown) other proteins What are reactive oxygen and reactive nitrogen species? - Ros and rns are unstable molecules that easily react with other molecules - Their effects are complex and depend on several factors: type of ROS/RNS, their contraction; their duration, location of production and the antioxidation system that removes ROS/RNS What do ROS/RNS do? Alter the 3D structure of proteins and change their activity (reduce ca release) Are they bad? No, signalling molecules. Too much is bad Mechanisms underlying reduce ca sensitivity of myofibrillar proteins and reduced maximal ca activated force following fatiguing contractile activity What role does intramuscular glycogen concentration have on development of fatigue? - Glycogen strong correlation between time to exhaustion and resting glycogen concentration.  - Depletion of glycogen impacts exercise capacity - There is a correlation between reduced SR Ca release od depletion of intramuscular glycogen after repeated tetanic stimulation of intact single mouse muscle fibers Changes in fatiguability following endurance training or hit Muscle hypertrophy increases the maximum force produced (1RM) – impact on the fatigue/exhaustion model