BPK 310 Study Question Post Midterm

Describe how IGF-1 is released and how it manifests change in response to resistance training. Include detail from Reading 9.1.

It is released from active muscle due to a load (resistance training, often high load, low frequency)→ muscle release of IGF-1 is more important for muscle specific adaptations • The paracrine signalling will influence satellite cells and neighboring muscle cells→ the nuclei of the satellite cells moves into the muscle cell→ Allows differentiation and proliferation of satellite cels into muscle nucleio which get incorporated into the muscle and aid in helping TF promotion, increasing mRNA # and increasing PS (Resistance training: hypertrophy) o Testosterone and GH →Both increase secretion with training o Testosterone will increase GH release • Increase muscle force—nervous system influence - GH stimulates the liver release of IGF-1 8-30 hours post-exercise o This will have more of a whole body influence (LIVER IGF-1)as oppose to muscle release of IGF-1 (more important muscle specific adaptations) o o Training can increase IGF-1 mRNA expression • Increase GH dependent/independent release (THROUGH TRAINING)!!!! • More IGF-1 release→ more hypertrophy Figure 19-4

Calcium ion is essential in excitation-contraction coupling within skeletal muscle. Describe the changes that can occur in relation to calcium with continued contraction. How do these changes relate to the onset of fatigue?

Normally Ca is very important for the contraction of the muscles but if we have a prolonged contraction there will be Ca in different areas of the cell, which will hinder the mitochondrial efficiency and a decreased gradient in the SR How they effect change (CAUSE)): Calcium accumulation decreases mitochondrial coupling efficiency - Some Ca+ helps stimulate kreb cycle and is beneficial (but over accumulation is not) - Accumulation requires NRG (atp) to get remove calcium - Causes oxidative phosphorylation uncoupling in test tube (amount of ATP coming out of a given amount of O2 is less than usual) ("gears are slipping" = less efficient) - Made worse by the fact that reduced Ca + sequestered by SR during fatigue Changes occurring: Sx of fatigue related to Ca (related to Ca release and/or pH effects on opening SR channels) Reason 1 and 2 are most important with 3rd being least important 1) Decrease free Ca+ (Less Release) EC coupling at T tubules/sarcolemma or SR changes Accum of Ca in sarcolemma (therefore decreased reuptake SR) Lactate anion interference with RyR Pi precipitation with free calcium (CaPi) 2) Decreased Responsiveness H+ interference with Ca+ binding site( TrC)(therefore w/e Ca+ is left has decreased impact) 3) Sensitivity (small Left to right shift) Given free Ca+ creates less force Further notes: Environment effects it: Heat/Humid= effects endurance performance (increases: Sweat/heat gain/dehydration and changes electrolytes) - decrease Q - uncoupling of mitochondria (Less ATP with same VO2) Fatigue is cumulative (yesterday's dehydration or glycogen depletion can effect today) (slight/non-full recovery in one day) Reduced circulation to muscles can result in glycogen depletion

What are the effects of aging on skeletal muscle fibre composition?

- Decreased lean body mass (muscle size peaks around 25-30 years old) -> impact quality of life - Loss of 8% / decade muscles strength after 45 Decrease in: - Size (diameter) and number of muscle fibers (sarcopenia=severe loss of myofillaments (contractile elements)) (less muscle=less activity=more atrophy=less muscle) CYCLICAL - Number of Type 2 a and b(Decrease is more rapid in the lower body)(decreased power and strength=cuz of decreased AP threshold (isomet and dynam) ) - LDH - Calcium-ATPase, Myosin-ATPase (effects Heart Muscle as well as skeletal) - Capillary/fiber ratio -> effects diffusion distance for blood (O2) (LESS BLOOD SUPPLY) - Oxidative enzymes: SDH, Cytochrome oxidase and MDH - Size and # of mitochondria - Size and number of motor unit - Respiratory capacity of muscle (happens cuz of less oxidative enzymes and decrease size/# motor unit)-> decreased [O2] gradient - ATP and CP concentration - Muscle is excitability - Decrease maximum contractile velocity Increased: -connective tissue and fataround the muscle (WHAT MUSCLE OF SMALL SIZEthat is left does not have same capacity cuz it has different things in it than before, MEANING LESS Myofillaments (contractile elements) and more fat instead - MORE SUBCUNTANEOUS FAT - Refractory period - metabolic economy and be more fatigue resistant

What factors are thought to be involved in fatigue during long-term, low-intensity exercise?

- Decreasesd glycogen (glycogen also helps conserve water and muscle shape)=evidence for glycogen depletion on exercise intensity shown in the blood glucose levels of Post absortive vs fasting. Also evidence shown by looking at different leg muscles. The muscles that we're more imporatant for the movement had more highly depleted - Fatigue at glucose below 3.5Mm - Anapleurotic stubstrates = decrease in kreb cycle intermediates = decline in reduced kreb capacity (low carbs decrease FFA utilization(b-oxidation)) "fats burn in the flame of carbs" Central Fatigue: cud be from pain and other psychological factors (Stechenov Phenomenon)

What factors are thought to play a role in fatigue during high-intensity work?

- High ATP turnover which cause CP depeletion(=high Pi leves) &High glycolytic rate (lots of glycolysis) - Causes low ATP/ADP ratio(ENERGY DIFFECIENCY)=decrease relaxation state and decrease shortening velocity - High H levels (Acidity)= impaired ATP regeneration and Pain= effects CNS fatigue (Also effected by Hypoglyemia and Hperthermia) - Impaired ATP regeneration=decreased force output (also effected by Pi levels)=periph fatigue Decrease ATP regen= decrease Relaction rate = periph fatigue Pi= inhibit PFK and interfere with cross bridging/attachment and detachment and force production (HIGH Pi is accompanied with high H2PO4 which have basically the same thing) H+= inhibit PFK/ interfere with Ca binding (PNS) / stimulate pain (CNS) **Check study question word document

Describe the changes that occur in skeletal muscle with endurance training. Include fibre type specific adaptation in your discussion.

- Increases in rec. freq. - No real change in X-sec area - Increases mitochon protein - HK increase, LDH (decrease in cytosol and increase in mitochondria)= 2 fold increase in O2 metabolism 1. Significant metabolic adaptations a. More ROS - Degree of adaptation depends on pre training status(WERE U AT THE HIGH/LOW END of genetic window)/intensity/durations Fiber Types - Increases of Succinate DH (MITOCHONDRIAL MARKER) most increase in FTb as oppose to FTa or ST for an endurance athlete (CHRONIC adaptation) but in sedentariy Succ DH is highest in ST. - With endurance training we will see: • 30% SDH • 28% CS • 25% beta-hydroxylacyl-CoA-dehydrogenase • 6% increase in capillaries • 31% increase in muscle fiber to capillary ratio • 23% increase capallaries in contact with fibers o Increase stimulation of capillary development o LDH (increase in the mitochondria, decrease in the cytosol) o SDH (kerb cycle) the response will vary with fiber type—involvement in training o Increase cytochrome c activity within fast twitch fibers o Increase maximium blood flow, capillary density, and potential for O2 extraction o The increase in oxidative enzymes mRNA several hours after exercise o No change in cytoskeletal factors (titin) o Increase in mitochondrial proteins/mitochondrial content and many glycolytic enzymes, cuasing a 2-fold increase in oxidative metabolism o HK increase - Training can change the histological and biochemical properties, but not the the fiber type distinction (a type 2 fiber will always be a type 2 fiber - Type 2 fibers become more aerobic in principles but are still lavelld as type 2

Draw the relationship between VO2 max and aging from 20 to 80 years, including both trained and untrained averages.

- Trained individuals have a higher VO2 max, but have a steeper slope with age than the untrained o At age 70: not as big differences between untrained and trained - age 20: the trained would be 77ml/kg/min and untrained 47ml/kg/min. - for age 80 trained 35ml/kg/min and untrained 33ml/kg/min. ⇒ individual variability in decline: genetics, training regime→rate of decline will vary - VO2 max declines ~30% from age 20 to 65 o Active 70 year olds can have a higher VO2 max than a sedentary 20 year old - Decrease in VO2 max: decrease in HR, stroke volume, power output capacity, fat-free mass and (a-v)O2 difference\ o Especially a decrease in muscle mass Note: Y-axis is VO2 max in L/min and X-axis is age starting with roughly 35 years and it goes to about 70 years Note: trained invidividual at age 60 has the capacity of 40 year old untrained Both VO2 max will decrease significantly but trained individual at a given age will have higher capacity

List and discuss the physiological adaptations that occur during heat acclimatization.

Acclimitization=adaption caused by NATURAL environment as oppose to acclimation (in lab enviro) Heat AND EXERCISE required to create acclimitization adaptation (either alone works) Adaptions: Within 2 week (most happen within 4-6 days)= Decreases: HR/ RPE (perceived exert)/ Core Temp/ Skin temp (at rest and submax exercise) Reduce mineral loss (ex. Sodium Chloride) that comes out in Urine and sweat) = Easier to maintain fluid balances between cells, extracellular fluid and blood Increased plasma volume(3% to 27% increase)=increased capacity for heat=increased sweating capacity (max goes from 1.5-4 L/hour )(LOWER SWEATING THRESHHOLD (U START EARLIER)=prevents early rise of Ct Decreased core temp at onset of sweating Decrease skin blood flow (cuz u want most of your blood in other places)=enhanced skin distribution of sweat THIS IS CUZ MORE HEAT GIVEN AWAY BY RADIATION AND CONVECTION HUMIDITY SPECIFIC ADAPTATIONS Fit individuals keep the adaptations for longer than sedentary Dry heat adaptations stay longer than humid heat adap Physiological change (Effect) Lower sweating threshold (Prevention of early increase in core temperature) Increase sweating rate ( 1.5-4 L/hour) (Greater evaporative heat loss, lower core temperature during exercise) Increased plasma volume (range 3%-27%) (Better control of blood pressure, lower heart rate, maintenance of stroke volume, increased VO2 max) Decreased skin blood flow -improve skin distribution of sweat (Increased heat loss by radiation and convection) Decreased loss of sodium chloride in sweat and also in urine (Easier to maintain fluid balances between cells, extracellular fluid and blood) Decreased core temperature at onset of sweating

Outline the physiological adaptations to chronic hypoxia

Acclimitizations=humans can adapt to live up to hights of 18000 and can adapt to short stays at higher Bicarbonate in CSF decrease cuz of excertion by kidneys: In response to decreased CO2 from hyperventilation - This helps Hb dissociation curve move to the right RBC 2,3-DPG increase (by product of glycolysis) =right shift of dissociation curve Decrease plasma V&increased Hemo/RBC/Hematocrit=increase O2 carrying capacity of blood Decrease in rest and submax HR (compared to acute exposure HR increase)=restores normal circulatory homeostasis Increased BP = increased tissue prefusion Increased Pulm BP=increased pulm perfusion (cud increase chance of Edema cuz of diffusion distance)=possible death (HAPE) Increased # and size of mitochon& in quantity of ox enzyme Increased skeletal muscle vasc=improved O2 transport Increased Tissue Myoglobin=increased cellular O2 transport Decrease catecholamine release=decrease lactate prod Brain - Vasodilation (High altitude Cerebral edema=NOT GOOD) (HACE) - Hypocapnea (vasoconstriction at brain) Balances vasodilation out Lungs - Increase size of Small Muscles of lung (arterioles) = this increases distance b/w alv & capillary INCREASED LUNG PAP = Increases chance of HAPE!! - Acclimatized submaximal exercise o HR still high, SV decreases o Q decreases 20-25% after 1-2 weeks

Describe the effects of work rate on sweating rate and rectal temperature.

As work intensity is increased -> core temp rises with increasing intensity -> rectal temperature increased and so did sweating rate increased work rate=increased metabolism=increased heat - Increasing sweat rate and rectal temperature both reach a plateau. o Benefits of increasing body temperature • Increase metabolic rate • Help lubrication • Diffusion rates o But don't want body temperature too high Sweat rate: proportional to work rate Sweat is primary means of heat dissapations during excercise, and since work rate increases body heat this causes hypothalamus to create sweating response Sweat rate is more related to exercise intensity(internal temperature) than environmental temperature (skin temperature) during exercise Rectal temp: Rectal Temp proportional to work rate o Core temperature variable at an absolute work load for each individual o But little variation when expressed as % of max capacity • Rectal temperature is as a result accurately reflective of workload when expressed as % of max capacity

Describe the influences of chronic exercise (training) on glucose uptake into skeletal muscle. Include appropriate detail for the proposed pathways using AMP-kinase.

Ca= Chronic increase in calcium stimulates transcription factors (ex. MEF2A, NFAT) these help the creation of GLUT 4 (PS through Trancrip/translat) as oppose to just getting it mobilized we're actually creating more - Causes higher levels of GLUT 4 (INCEASED GLUCOSE UPTAKE CAPACITY) protein and Mitochondrial enzymes AMPK(using an ANALOG AICAR)= increases GLUT 4 protein expression and HK activity in muscle With AMPK= SDH, CS, MDH and cytochrome C will increase in fast-twitch muscle only ENDURANCE TRAINING: CAN CAUSE THESE INCREASES IN Ca and AMPK releases which has similar effects as the Ca and AMPK studies= Increased GLUT 4 Creation - May improve glucose tolerance during early stages of the development of type 2 diabetes by stimulating insulin sensitivity or increase GLUT-4 migration ACUTE CHANGES WHEN PROLONGED CAUSE CHRONIC CHANGES

Outline the potential sites of fatigue in the periphery.

Causes are sometimes specific (glycogen (site: glycogen stores)/ Ca delpletion) Sometimes Tough find exact area/source of fatigue cuz of Compartmentalization (ex. ATP may be low at Myosin head but adeq every where else) and Diffuseness of Fatigue (Dehydration/disturbance of homeostasis/u can often find CORRELATES of fatigue as oppose to CAUSES) Specific Sites ex.: Motor End PlateNeuromuscJunctio=increased K in Extracellular / failed end plate transmission / decreased Ach release Sarcolemma=inhibition of AP by increased interstitial K+ SR=1) failure of AP b/w T-tubule and SR 2) changes in Ca+ channels3)decreased sequestering of Ca from SR and inadequate re-uptake actin myosin X-bridge: 1) H+ competes with Ca for troponin binding site 2) Pi and H slow myofibrillar ATPase activity 3) decreased myofibrillar sensitiyvity to Ca4) H causes decrease in force development 5)metab accum inhibit force prodocution 6)diprotenated Pi ¬inhibit muscle contration 6)AMP levels effect force development Glycogen stores

Discuss the physiological changes that occur in response to chronic cold exposure.

Change in Shivering Threshold= Maintain temp w/o shivering or less shivering - Inc. thyroid hormone (tissue more sensitive to norep and epin)= - Uncoupled O2 phosphorylation=Heat released w/e ATP formed - Leptin -> released from adipose (fat) - Stim. SNS Released Sleeping In the cold=depends on Non-shivering thermogenesis - Aboriginal people of Australia (vasoconstric periph=decrease heat release (convec/radiation) from periph Temp of hands/feet - Acclimitization=temp maintained (no temp decrease like unacclimatized (we keep heat in the core) Intermittent Vasodilation to periph (hunting response) (CIVD) cyclical response (where u release a lil bit of blood and then take it back and so on (into hands/feet and )) - CIVD (Cold induced Vaso dilation) only happens when u have warm core - Habituation as well (BECOME MORE TOLERANT) Normally: Warm Body allows AVA`s in the hand open and blood flows through the hand increasing hand temperature. But the cold causes Arteriovenous ANatomoses to close. After Chronic exposure the body does CIVD (intermittent vasodilation)

List and explain the factors involved in heat loss.

Clothing and Air temp effect capacity for heat loss Heat Loss: Radiation/Conduction/Convection/Evaporation (humidity screws it up) (environment) Hydration status= heat regulation goes down as water goes down cuz u can't sweat and use the sweat as the sweat on the skin as fluid to hold heat till it evaporates. (EVAPORATION) Clothing=create a air pocket around you, you won't allow new air to come by your body to pick up the heat, instead the same air particles will be stay there and not let you release more heat into the air. - Radiation: heat in the form of electromagnetic radiation—60% of heat loss at room temperature at rest - conduction: transfer of heat through contact o rate of transfer depends on temperature gradient and conductive properties of surface - convection: conduction to/from air or water o depends on body surface area exposed to surrounding medium and the flow of that medium o more rapid in water (~25 times) o heat loss is much greater in wind and moving water Physiological responses to heat gain: when core temperature above set point (37 degree Celsius) anterior hypothalamus elicits physiological cooling mechanism - evaporation: o 70% of heat loss in the heat o Heat absorbed by sweat as it evaporates from the skin -convert liquid to gas you need heat to do this o 1gm sweat=2411 J (0.58 kcal) - Sweat is only effective for cooling if it evaporates o Max sweat rate is ~ 1.5 L/hour in sedentary untrained individual o Max rate improves to about 4L/hour with exercise acclimatization to hot humid environments o Eccrine glands—cooling (forehead, back, palms) o Appocrine glands—odours (axillary and pubic regions) - Humidity o Heat exchanged with environment by vapour transfer o Driving force is difference in humidity - Relative humidity—given as a percentage o Saturated vapour pressure is the vapour pressure at which no more water can be held - Vasodilation—increase peripheral blood flow in the heat, increase heat loss by convection and radiation, and allows water to travel to skin to be disposed of through sweat.

Compare and contrast the training adaptations accompanying weight training in elderly versus young individuals.

Compare: - Relative strength game is similar (ex. 30% gain over a certain period of time will be same with old and young) (absolute change is less but % change similar) - Improved cognitive func/self efficacy/reduced depression - Prevent muscle loss (INCREASED CS area (15%-40% increase and its in both type 1 and 2) (increase in force production) - Prevents bone mineral loss - Posture stable/decrease risk of fall/fracture - Improve joint health/flexibitly Principle of exercise prescription is the same (progression, overload, individual differences, specificity, reversibility) Study: men 60-72 years old→resistance training resulted in: muscle fiber hypertrophy and performance improvements - 110% increase in force development for 1 rep max contractions of knee extension after 12 weeks training - Increases quadriceps area (9%) - Increase CSA of type 1 (~34%) and 2 fibres (~28%) in VL muscle Contrast: - DOES NOT RETARD AGING PROCESS (ALLOWS PERSON TO PERFORM AT HIGHER LEVEL) - Weights being done obviously less resistance to start off (then progress) (ex. Theraband) - With program= Elderly: extra caution with overtraining, • reduces risk since their capacity is less than young people

Explain the diffusion limitation at altitude. Redraw Figure 23-6 (23-7b) (textbook) as part of your explanation.

Decrease O2 in inspired air=decreased alv O2=decreased Art=Decreased Venous O2 Decrease ambient O2 and decrease in alveolar O2 BUT difference between Ambient and Alveolar getting smaller=decrease [O2] gradient= decrease capacity to bring in air (LESS DRIVING FORCE) Exercise - (at sea level, exercise causese slight increase alv O2 cuz of hypervent) (drop in venous) - At 5000m (increase alv O2 (ALSO CUZ OF HYPERVENT) and DECREASE in ART O2) (drop in venous) ART decrease cuz: at sea level theres large [O2] gradient/pressure gradient. This gradient allow for PAo2 and Pao2 to equilibriate quickly (withing 0.2 seconds) BUT at high altitude Gradient is much smaller=take longer for equilibrium (DRIVING FORCE IS LESS/ LESS STEEP SLOPE) to happen (takes around 0.6 seconds), Since during exercise our ventilation rate is very high when we breathe in around 0.3/0.4 seconds the PAo2 and Pao2 have not yet equilibriated

What are the physiological effects of acute exposure to altitude?

Decrease VO2 Max/increase in submax VO2 (cuz of higher submax Q and HR) - same workload req. higher VO2 & same workload becomes higher percentage of max Decrease in Max VE (increase at submax work rate (given work rate is gonna need more air cuz the [O2] in air is lower) - Barometric pressure going down therefore O2 diffuses more through the air=lower [O2] in air Lower O2 saturation of Hb(ORIGINALLY SHIFT TO LEFT cuz of Low CO2 then shift back right when Bicarbonate leaves through urine) Lower Arterial O2 & CO2 RPE goes up Drop in (a-v)O2 SV drop submax but same at max Increased catecholamine secretion AMS=headache/nausea/irratible/weakness/poor appetite/disturbed breathing (SLOW ACCENT IS BENNEFICIAL)

What are the cardiovascular changes associated with aging? In your answer describe the functional significance of these changes on aerobic exercise capacity and performance.

Decreases in: - Blood plasma and RBC volume -> decreases Venous return therefore decrease EDV and SV(VARISCOE Veins= problems with one way valves in veins that are helping against blood flow with gravity) - Capillary to Fiber ratio -> decreased muscle blood flow & increased diffusion distance - Cardiac Compliance -> Decreased Pre load -> decreased diasctolic filling ->SV hasrelies more on frank starling mechanism=) - Endothelial disfunction = Decressed NO -> decreased BF control Autonomic reflexes that control BF are reduced Poor circulation at rest=cold periphery & during exercise HOT PERIPHERY MORE orthostatic intolerance (fainting when u stand up) = blood rushes away - Na-K pump activity ->decread MGMT of cell H2O and electrolytes - Elasticity of blood vessels ->INCREASED peroph resis (Cuz of connective tiss changes in blood vessels)->increased SBP (NOT DBP) and AFTERLOAD - Myocardial Myosin-atpase & Ca Atpase actitivity -> decreased myorcardial contractility - Decreased symp stim of SA node -> HR!! DECREASED VO2 max (declines 30% from 20 to 65) Trained and Untrained both have similar declines Decrease SV: -decreased capacity of heart to pump blood - SV and Q are less at relative and absolute intensity - decrease Contractile strentgth : CUZ OF Ca-ATPase (pump Ca back into SR) and Myosin Atpase(stimulation and production of force)& cuz of myocardial ischemia -Heart wall stiffen=decreaed diastolic filling -blood vessel elasticity=increased periph resistance -DECRASED HEART MASS - slower relaxation of VENT WALL!!! HR: - lower at relative int but same at any absolute intensity - Cardiovascular drift higher = large shift of HR/SV at stead intensity exercise= (LOST CAPACITY TO PROPERLY DO HOMEOSTASIS) - Longer Recovery time to rest BPM from after exercise - Decreased: Beta adrenergic responsiveness= DECREASE MAX HR &DECREASE CONTRACTATILITY - Max HR is also decreased and there is more variability (people older than 60—105-200, while HR prediction gives 160)(PREDICTION EQUATION IS FLAWED) (a-v)O2 Decrease in: - Capillary to fiber ratio (higher diffusion distance) - Decrease in Total Hb (decrease O2 carrying capacity) - Decrease in respiratory capacity (Cuz of decrease in Mitochondria density of muscle and decrease in ox enzymes) -> decrease [O2] gradient -> pulling less from capillaries - decreased arterial oxygen saturation→decreased concentration gradient → as blood moves by, can't pull out O2 - Capacity of autonomic reflexes (stress system) that control blood flow is reduced with age: greater blood flow to the skin for the elderly →ability to extract O2 at the muscle is impaired(DURING REST BLOOD GOING TOO SLOW DURING EXERCISE GOES TOO FAST)

Define (a - v)O2 difference and provide reasonable numbers and units for maximal activity of a 20- and 65-year-old subject. Explain what is thought to contribute to the changes in (a - v)O2 difference with aging. At a given absolute workload, would you expect the younger or older subject to have a higher (a - v)O2? Why?

Define: Diffrence in O2 concentration between arterial and venous blood. Effected by the extraction of O2 as it moves through a tissue bed. Decrease Number with Age 1. Decrease ability to extract O2 2. Leave a lot more O2 in the blood 20 year old = 16% of volume 12% (65 years) (ml O2/ 100ml of blood) At 20, leave about 4%, and at 65, leave about 8%, twice as much. 20 year old: 150 mL/L 60 year old: 140 mL/L Cuz of Decrease in: - Capillary to fiber ratio (higher diffusion distance) - Decrease in Total Hb (decrease O2 carrying capacity) - Decrease in respiratory capacity (Cuz of decrease in Mitochondria density of muscle and decrease in ox enzymes) -> decrease [O2] gradient -> pulling less from capillaries - decreased arterial oxygen saturation→decreased concentration gradient → as blood moves by, can't pull out O2 - Capacity of autonomic reflexes (stress system) that control blood flow is reduced with age: greater blood flow to the skin for the elderly →ability to extract O2 at the muscle is impaired(DURING REST BLOOD GOING TOO SLOW DURING EXERCISE GOES TOO FAST) You would expect an older person to have a higher (a-v)O2 at a given absolute workload, BUT A LOWER MAX (a-v)O2 o For submaximal exercise: cardiac output is lower and to maintain VO2 the (a-v)02 is going to be higher. • Main reason why Q is lower: lower SV ⇒ Basically saying that the older person is working at a higher relative % of their capacity

Define and describe central fatigue; include one well-documented piece of evidence that supports the theory of central fatigue.

Definition: -fatigue w/o muscle itself being fatigued (more mind as oppose to matter) -pain can effect drive -when external stimulus can increase force output=central fatigue indication: test by comparing force output during fatigue to force output during max external stimulus Effected by psychology: Athletes who train can minimize sensory inputs and reach true performance limit Evidence: Stechnov Phenomenon: faster recovery with distraction or "active pauses" - After work bouts (During rest phase) light phys activity or mental activity is done before

Briefly relate the concepts you have just described to myoplasticity by describing how an acute response to exercise can result in a long-term adaptation.

Different training causes different long term adaptations; however there is only limited ability to change fiber types ACUTE CHANGES WHEN PROLONGED CAUSE CHRONIC CHANGES Continued acute changes in the microenvironment (continued increase in Ca and AMPK) 2. Leads to chronic microenvironment changes (Ca high, which stimulates TF (NFAT, MEF2A) and AMPK high which will increase GLUT-4 gene expression) 3. Causes an increase in GLUT-4 synthesis since it is a protein and HK activity 4. This changes the phenotype of the muscle (more GLUT-4) 5. And will impact the microenvironment◊better response by more glucose coming in since were sending more GLUT-4 to the surface - We can make intermediate transitions in MHC (changes from type 2b to 2x or 2a to 2x ect) WE CANOT GO FROM type 1 to 2 - WE CAN change biochemical and histological properties of the fiber (ex. Amount of mitochondria in it) - Elite athletes usually have the proper types of muscles to being with. (sprinters 2b) and (endurance athletes type 1) Increased AMPK through exercise (or AICAR) = increased Citrate synthase (CS) and dehyrogenases -> increases fast twitch muclse cell growth.

Declines in creatine phosphate (CP) are often associated with fatigue; ATP, however, remains fairly high until exhaustion. Summarize the evidence for CP decline with fatigue, and describe the possible reasons for ATP maintenance.

Evidence for CP decline: (Cp mmols per 100 g of dry muscle drops as intensity of exercise increases, rate of ATP synthesis by CK also drops indicating CP decrease a. CP declines because of the very rapid ATP turnover rates such as in the shot put, so the CP is broken down by CK to form ATP quickly b. Look at figure 33-2a: 1. CP level will decline in 2 phases - The first drop will be rapid and then the second drop will be slower - Both the severity of the first drop and the extent of the final drop will be related to work intensity 1. The higher the work intensity the greater the depletion of CP and more O2 will be needed to recovery to replenish the CP 2. However, with ATP there is no steep drop and the ATP is well maintained - Compartmentalization: even if there is a decrease in the ATP around the myosin ATPase we are not able to detect it because we cannot look that specific into the cell - Down regulation theory/protection theory: muscle cell shuts off contraction—with ATP depletion in favor of maintaining ion concentration gradients and cell viability 1. Need ATP to pump Ca back into the SR, restore Na/K gradients) 2. Need ATP to release the actin and myosin from one another(for muscle to relax) 3. Because of decreased CK activity you will not be able to rephosphorylate ADP to ATP and ATP levels will drop 1. The creatine kinase also allows for very rapid recovery →we can see for the same work rate that ATP is well maintained relative to the CP →Drop in ATP is a lot less significant →rapid recovery of ATP at the end of the event

Using the phosphagen system as a source for environmental changes, describe one example from each of the two categories of peripheral fatigue. Include a description of how your example changes with exercise, and how it could contribute to fatigue.

Exhaustion: at rest ATP synth rate is high cuz theres available CP can become restored and other substrates (Glycogen/glucose) can help restore ATP during exercises CP levels decline (2 phases=fast 1st and slow 2nd)), this causes decrease in ATP synth rate (by CK); ATP level is better maintained than CP, We want ATP stable cuz its more important than CP, we need it to contract and more importantly relax muscle ( u don't want permanent contraction cuz of insufficient ATP); ATP also need to maintain maintaining ion concentration gradients and cell viability (keep pumping Ca back in to SR and aids Na/K pumps) comparmentiliation: we don't know exactly where ATP has decreased (we have large view not small sections, there cud be decreases in specific areas as oppose to macroscopic decrease) Accumulation: accumulation of Pi and H2PO4 (both act similar to proton)=indicateds non-steady state=fatigue-inhibit PFK (affects glycolysis) / interfere with (Myosin actin )X-bridging, attachement, detachment and force prod

Define peripheral fatigue distinguishing between the two major hypotheses.

Fatigue: Inability to maintain a given exercise intensity or power output (periphal: same/constant stimulation, decreased force output) (voltage of action potentials stays the same but force production decrease or ap has to continualty increase and causes no increase in force) (measure EMG vs Force) - Fatigue: 1) RARELY complete (can work at lower output) 2)recovery with rest 3) decreased force and velocity of contraction/prolonged relaxation time -Exhaustion: (Depletion of substrates) phosphagens (ATP/CP), glycogen/glucose -Accumulation: PH, phosphate, calcium, potassium, "CAUSES FOR FATIGUE ARE INTERACTIVE AND MULTIFACTORIAL " - Ryan Dill

Define the following: homeotherm, core temperature, hyperthermia, and hypothermia.

Homeotherm: organisms that have ability to tolerate variable environmental temps by TIGHTLY REGULATING OUR INTERNAL (CORE) TEMPPhysiological changes=(SHIVER/SWEAT) WE also use behaviourial changes such as stomping our feet or rubbing our hands together Core Temp:defined as temp of hypothalamus range: (normal 36.5-37.5) (usually seen as 37) - In experiments core temp is estimated by rectal/esophageal (more common) temp (rectal is flawed cuz its effected by muscles mass in the area which gives off/picks up heat from/to internal environment VERY SLOWLY - Oral temp (effected by cold air) and tympanic temp (effected by skin temp) also used ALI:: Normal core temperature: 36.5-37.5 1. Exercise: core temperature can exceed 40 →rise is proportional to intensity 1. Often goes above 40 if we don't have adequate heat dissipation 2. Pregnancy→shouldn't rise above 38.9 2. Temperature does remain fairly constant at rest 1. Skin temperature is influenced by environment, metabolic rate, clotting, and hydration state Hyperthermia= overheated, elevated body temperature due to poor thermoregulation→Ct over 41 is where brain cells start to deteriote Hypothermia: Core Temp At temperatures<34 →cellular metabolism slows, which can lead to unconsciousness and cardiac arrhythmias Mild=32-35 Moderate 28-32 Severe= <28 - hypothalamus ceases to control body temperature at extremely low temperatures (less than 30 degree C) o CNS depressed o Lose ability to shiver o Sleepiness—coma o Reduced metabolic rate—decreased temperature - Cardiovascular o Central blood volume will decrease o Exacerbated by: • Inadequate fluid intake • Plasma sequestration • Cold diuresis (PEE MORE) - Hypothermia is possible during endurance exercise events o Heat loss is greater than production o Glycogen depletion—blood glucose declines, CNS functioning declines

Using Figure 19-3 in the textbook, discuss a hormonal or metabolic example from the textbook that is involved in muscle adaptation. Use sufficient detail to demonstrate your knowledge of how changes in the microenvironment result in adaptation.

Hormones—independent of nutrition Hormone=IGF-1 (Insulinlike Growth Factor 1) • Mediates growth hormone effects Microenviroment (intracellular milieu everything inside cell) & immediate Extra cellular space(hormones and cytochymes)) Change=Differentiation and incorporation of satellite cells from paracrine signaling of IGF-1; satellite cells differentiate into muscle nuclei move into muscles. Note IGF also does Autocrine signalling Proteins: More nuclei means higher potential for: Promotion by TF More mRNA & more PS (prot synth) Phenotype: increased hypertrophy through PS Note: GH stimulates the liver release of IGF-1 8-30 hours post-exercise • More of a whole body influence, • but active muscle itself will release IGF-1, which more specifically helps the muscle itself

How can we prevent thermal stress in the workplace and during exercise in a hot environment?

Hydration/electrolyte balance= 0.4-0.8 liters/hour in marathons & after excersie 1.5L/Kg weight loss With regards to exercise=precooling (ice jackets/ice seats ect.) Acclimitization=over 4 days - 2 weeks Don't wipe sweat off ur face/body, let it stay there till it evaporates, otherwise u'll lose more sweat. Proper clothing (LESS clothing usually/breathable material), don't overdress, (increased clothing will not allow heat to escape cuz it creates an air pocket - Wet bulb globe temperature (WBGT) index is most common index for heat stress to protect workers o Indication of heat storage, then determine how long they can work in environment, work/rest ratio o WBGT= 0.7tnwb + 0.2tg + 0.1ta • Tnwb: temperature of naturally ventilated wet bulb thermometer • Gives indication of: o Humidity o Potential evaporative heat loss o Air flow • Tg: 150 mmHg diameter black globe temperature • Gives indication of radiation • Absorbs radiative heat • Ta: air temperature (convective heat) o 0.7+0.2+0.1=100 % of influence, % by which components contribute to the total o WBGT index is adjusted for clothing insulation o Graph of core temperature vs. WBGT -each workrate stays relatively stable at a given Ct but when it is in the prescence of a threshold WBGT the Ct will rise dramatically

What would be the effects of hypobaria on a miner living and working in an open pit mine at 4300 m above sea level?

Hypobaria: low ambient air pressure Smoggy air can have a negative effect on physical performance, health, and well-being. With hypobaria, we see hypoxia (O2 at 21%, so decrease ambient air P and decrease PO2), so see Q 5 for chronic adaptations to hypoxia. They will have more erythrocytes than someone at sea level, more Hb and hematocrit to compensate for decreased PO2. This allows the optimal O2 carrying capacity by blood without making blood viscosity too thick for adequate blood flow. Chronic mountain sickness (CMS) can occur after years at altitude. Live high-work high: see increase VO2 at altitude, so will be able to perform potentially well at altitude.

Discuss the role of the hypothalamus in temperature regulation. How do the anterior and posterior hypothalami differ in function?

Hypothalmic Control= Heat production (shivering) or heat dissipation (evap) Anterior= elicits cooling response when temp above 37 degrees & cause SHIVERING when temp goes below 37 degrees HEAT - Causes sweating= sweating only works if it evaporates ( if you wipe the sweat off u'll just sweat more cuz heat exchange wont happen) - Come from Eccrine Glands (release the sweat) Appocrine Glands= produce smell (odour) (gooch/armpits) - Vasodilation → increasing peripheral blood flow and heat loss via convection/radiation increases relative humidity, humidity, evaporation COLD - Shivering= increase METAB function 5x Vasoconstriction=decrease blood going to periph=decrease in convec and radiation heat loss Piloerection (arrector Pili muscle)= hair stand still (goosebumps)=trap still air around skin (act like sweater=create air pocket) Posterior Hypothalamus→ also elicits shivering for the cold - Stimulates release of NE → FFA mobilization = increase in metabolic heat production - Increases thyroxin indirectly through thyrotropin releasing hormone which causes release of thyrotrophin from the pituitary and acts on the thyroid to release thyroxine Both anterior and posterior hypothalamic increase NE release → increased thyroxine, metabolism

List and explain the factors involved in heat production.

Hypothalmic Control= Heat production (shivering) or heat dissipation (evap) Heat and cold receptor on the skin/periphery • As head temperature increases, we will increase the number of calories lost through evaporation past 37 degrees Celsius • When core temperature drops below set-point (37 degree Celsius) anterior hypothalamus elicits physiological warming mechanisms (EXERCISE/MUCSLE CONTRACTION(shivering)/Hormones (thyroxin)/Symp stim/Q10 effect (every 10 degree increase means double metabolism, as we're getting hotter we're metabolizing more) = Metabolic Rate=O2 metabolism gives off heat as by product - Shivering: increases metabolic heat production by up to 5 times; onset is determined by skin temperature—cold is a stimulus Radiation/Conduction (touch a surface, DIRECT CONTACT)/Converction (air or water) (ENVIROMENT) - Radiation: heat in the form of electromagnetic radiation - conduction: transfer of heat through direct contact o depends on temperature gradient and conductive properties of surface - convection: conduction to/from air or water o depends on body surface area exposed to surrounding medium and the flow of that medium o more rapid in water (~25 times) o heat loss is much greater in wind and moving water SOME PROCCESES HELP MAINTAIN WHAT HEAT THE BODY HAS & PREVENT FURTHER HEAT LOSS Vasoconstriction: constriction of vascular smooth muscle cells reducing peripheral blood flow and heat losses via convection and radiation Piloerection: hair stands on end in order to trap still air layer against skin o Arrector pili muscles attached to the hair follicle involuntary contract

Summarize the impact of inactivity or immobilization on muscle size and strength. Why do you think these changes occur? Using evidence from the textbook, discuss the time course and extent of the adaptations you describe.

Impact: - Decrease in rec frequency and load - Reduction in metabolic and exercise capacity (WITHIN 1-2 weeks) - COMPLETELY (extent) LOSE UR ADAPTATION WITHIN MONTHS (ANY IMPROVEMENTS IN STRENGTH GO AWAY COMPLETELY (MUSCLE DECREASE PLATEAU AFTER 2 weeks) - VO2 max decrease (25%=extent) - HIND LIMB SUSSPENSION STUDY = Decrease in Ms size and X-sec area (decrease in metab proteins in muscle) (drastic loss with 2 weeks, don't lose as steeply after that) - Decrease in metabolic content for mitochondria Evidence: - SPACE FLIGHT, muscles not being used (less gravity)=atrophy) - (Immobilization studies=Hind leg suspension in rats) WHY IT HAPPENS: Inactivity/Detraining Why: By mechanisms of myoplasticity → acute conditions of inactivity will cause changes in the microenvironment→chronic inactivity will result in adaptations to accommodate that state of intensity were imposing on our body (inactivity) - So if you're being sedentary, it's like you're training to be sedentary, so you'll get good at being sedentary. It's economical to not use the body's resources for muscle development and maintenance if those muscles aren't going to be used.

What are the effects of endurance training on aged skeletal muscle? Compare these to adaptations in young individuals with endurance training.

Improvements are similar to younger people but it cannot prevent inevitable decline caused by age - Maintain CV function & increased exercise capacity - Decreased risk for HD, diab, insul res, and certain cancers - Slow down age related inc. of ROS COMPARE: similar improvements b/w YOUNG AND OLD!! (6 months=20% inc of VO2 max) - Decrease Submax HR at absolute load - Decrease SBP in rest and submax - Fast HR recovery from excercise to rest - Fix/improve some ECG abnorm - Increase SV and Q CONTRAST: 20ml/kg VO2 max is good enough for elderly ATLEAST!!! - Well structured plan=give this to them within 3 months - With people with pathologies (ex. Heart Issues) it might be tough to train them at the same rate and give them the same % increases as youth - MASTERS ATHLETES: are higher than matchedyoung athletes in a lot of markers (Oxiddative enzymes and capillaries/fiber capillaries/area) - - 30% more succinate dehydrogenase (involved in both Electron Transport Chain and Kreb Cycle) - 28% more citrate synthase (involved in 1st step of Kreb Cycle) - 25% more beta-hydroxyacyl-coA-dehydrogenase (involved in 3rd step of beta-oxidation) - 6% more capillaries - 31% more capillaries per fiber - 23% more capillaries in contact with each fiber

What factors account for the increased submaximal VO2 for a given work rate in the cold?

In submax VO2 (ie. Work) increased at given low intensity - Increased shivering=Increased metabolic cost Shivering necessary cuz of Higher heat loss - inc skin and muscle blood flow during exercise in any temp - GREATER THERMAL gradient in the cold results in greater heat loss. Wet clothing in wind= VO2 requirement increased 15-20% (cuz ur body needs to make more heat to maintain core temp) BODY May also be increase in non-shivering thermogenesis—due to increase catecholamines (stress) and leptin Extreme cold: increased ventilation due to stress, sympathetic stimulation so the energy cost of breathing harder will increase our VO2 At submax, we aren't working at high enough metabolism, so significant amounts of heat isn't produced, so cold environment means heat gaining mechanism need to kick in - NOTE: VO2 MAX is unchanged so we are producing enough heat from exercising so we don't need extra energy use for shivering

What metabolic changes accompany aging? Describe their effects on energy provision during activity and onset of fatigue.

Increase in the % body fat/decrease in the lean body mass due to metabolic changes 1. With sarcopenia, we lose muscle, and since fat is less metabolically demanding than muscle, we have a decrease in metabolism 2. Resting metabolic rate (RMR or BMR): small component of decline is associated with decreased muscle mass b/c muscle is a high metabolic demanding tissue 3. Selective loss of type 2 fibers →decrease available strength and power 4. Losss of biochemical capacity with age→decrease in ATP and CP concentration and decrease in glycolytic enzymes (LDH)→less energy can be produced(NRG PROVISION) Less muscles, less type II / higher type 1 vs type 2 (type 1 more endurance based vs type 2 more power/strength) 1) (MUSCULAR COMPONENT)Type 1: Slower Force Relaxation/ Force fusion at lower freq/(BECAUSE OF THIS LOW FREQ< these muscles require less energy to do wut they need to do) type 1 have higher metabolic economy 2) Neural COMPONENT: decreased motor neuron discharge rates (less contraction and less force produced=LESS METABOLIC demand) ALL LEADS TO= HIGHER METABOLIC ECONOMY=LESS FATIGUE 1. Aging involves diminished capacity to regulate internal environment 1. Ability to regulate metabolism during acute environment 2. Aging may be related to free radical function from oxidative metabolism. 1. Mitochondrial theory of aging: 1. Build of free radicals/oxidants in mitochondria→damage the mitochondrial DNA(superoxide radical)(also act on protein and lipids)→increase activity with exercise→increase O2 flux and more free radicals produced and age faster 2. Mutations due to guanine oxidation→impairs adenine instead of cytosine 3. Mutations Hydroxyl radical causes DNA lesions 4. CHANGES THE GENETIC FUNCTION 3. Mitochondrial activity in the cells slow down with age 1. Decreased availability of mitochondria→decreases availability of ATP→early onset of fatigue for a given activity 4. decreased mitochondria →decreased aerobic enzymes→decreases our capability for aerobic metabolism, affecting our CV abilities. 1. Decreased oxidative metabolism in mitochondria leads to increased anaerobic metabolism and lactic acid production. Acidosis in skeletal muscle can be perceived as muscular fatigue.

Describe the changes that occur in skeletal muscle with resistance training. Include fibre type specific adaptation in your discussion.

Increase reccruitment freq and LOAD of/on muscles Hypertrophy -> increase in max force produces (Strength) Decrease Cap density (13% drop) and Mito protein (25% decrease) = Low O2 efficeincy for delivery. HIGHER area of muscle cuz of hypertrophy but the capillaries/fiber haven't increased therefore the area thtat these capaliraies have to give O2 to is much larger Mitochondrial volume/myofibilar volume is also going down, since muscle is growing and mitchon aren't growing at all or at the same rate! - cytoplasmic volume increasing, so contents of cytoplasm outside mitochondria going up, which is what's stimulating hypertrophy THEREFORE U SHUDN't just do resistance training (U SHUD COMBINE IT WITH ENDURANCE) Better force velocity relationship - Move same sub max load at a a higher velocity -> INCREASED POWER!!! (TIME FACTOR) - (GRAPH) THE FASTEST WE CAN MOVE IS STILL THE SAME BUT the max force we can move is higher - enhance power output (time factor) Increase of X-sec area happen in both type 1 and 2! (type 2 has a lil more growth) a. type 2: 33% b. type 1: 27% increase in fibre area c. ~30% increase in strength Type 2x shift to 2a MHC's (FASTEST MHC's are REPRESSED) Specific Force doesn't change much as muscle size increases. The intial increase that happens in specific force is cuz of neural adaptations Fibre type specific adaptation

What is the effect of cold on metabolic energy provision during exercise in the cold?

Increased use of Carbs during Excercises=muscle glycogen decrease faster in light exercise=INCREASED LACTATE PRODUCTION - Overtime=hypoglycemia=suppressed shivering=(higher likeliness of hypothermia) Decrease FFA utilization cuz less blood going to adipose tissue to pick up FFA and take it to muscle - Catecholemine rise (CAUSES INCREASE IN LEPTIN RELASE) is NOT enough to create increased FFA utilization CUZ of DECREASD SUBCUTANEOUS circulation ALL OF THESE THING get worse with fatigue/sleeplessness and underfeeding

Describe the influences of acute exercise on glucose uptake into skeletal muscle. Include appropriate detail for the proposed pathways using AMP-kinase.

Insulin and muscle contraction help GLUT 4 increased Increased GLUT 4 at cell surface (migration of vesicles with glut 4 on them to surface from intracellular pools)=HELP GLUCOSE FACILITATED DIFFUSION o Insulin binding to IRS-PI3-K, which will cause GLUT-4 inside vesicles in the cell to migrate to the sarcolemma muscle membrane • Done by PIP2→PIP3→activates PDK1→Akt→has influence on GLUT 4 Muscle contraction= increases Calcium and AMPK increase - Ca acts trhough CAMK (Calmodulin Dependant Protein Kinase) stimulates migration of GLUT 4 to surface - AMPK regulated by ratio of ATP/AMP and CP/Creatine= ACUTE AMPK stimulates migration GLUT 4 to surface from vescicles WE MIGHT HAVE 2 DIFFERENT POOLS OF GLUT 4, we stimulate one through Calcium and one through insulin. We see this through the additive effect of the 2 together. 1. Type II diabetes may involve errors in insulin signalling or the downstream stimulation of GLUT-4 migration 2. With exercise, delivery, uptake, and metabolism of glucose need to increase

Summarize the principle of myoplasticity. Use and describe the terms protein turnover, phenotype, isoform, and genotype in your discussion. Include details from textbook, Figure 19-2 in your description.

Myoplasticity: Myoplasticity is altered gene expression that can result in an increase (up-regulation) and a decrease (down-regulation) in the amount of specific protein the molecular basis for training adaptations of muscle - Changes QUALITY and/or quantity (hypertrophy) of protein!! TRAINING EFFECTS where you are in your genetic window=are u at the top end or bottom!!! - High potential to alter gene expression and therefore change the (INCREASE/DECREASE amount of specific proteins) - MUSCLE LOADING=CHANGES RNA activity (TRANSLATIONAL Capacitiy and TRANLATIONAL Efficiency)=Protein synth=hypertrophy=INCREASED # RNA= INCREASED transcriptional efficiency (transcriptional rate per myonuclei) & increased Trancrip Capacity( satellite cells combine with muscle fib=INCREASE # of muscle nuclei) LIFESPAN OF AN MRNA effects how much protein is made = ALL OF THIS MEANS MORE HYPERTROPHY!!!!!!! GENE EXPRESSION AFFECTED by hormones and loading (load effect Trans. fact.)=effect translation and transcription=changes in PS ALL OF THIS helped transcript factors which effect promotion DIFFERENT demands (amount and type endurance (high freq/low sus load) vs strength training (low freq/high load) cause different environments in the muscle=effect different gene expression Protein Turnover=resynth and breakdown of protein (AA pool to produce protein and full peptide & poly peptides to give off AA) reflects HALF LIFE OF PROTEIN (TIME Fram for existence) ("how long is a given protein around for before it degrades and we have to synthesize more!!" PROCESS OF HOW EVERY PROTEIN IS TRANSCRIBED(DNA/mRNA, TRANSLATED (mRNA to Protein) and DEGRADED (TEXT BOOK) - Level of the cell protein governed by: o Balance of synthesis/degradation o Precise regulation of content through control of transcription rate • And/or breakdown rate - Mechanism provides the capacity to regulate structural and functional properties of the muscle - Note: o Actin • breakdown and synthesis through an increase in loading • BUT, we will have a free amino acid pool in the muscle • De nova synthesis→Free AA pool→oxidation o Interachange with blood (circulation) • Once in circulation, which can be added from diet or from breakdown from other tissues, it can be transport where needed Proteins: 20 % of the muscle is protein and the balance in water and ions o All proteins can be regulated by altering gene expression • Actin, myosin, contractile apparatus, titin (shape of the sarcomere and retain length when contracting) • Enzymes such as kinases Phenotype: outward/observable characteristics of muscle (phenotype reflects the underlying genes) (EXPRESSION OF GENES) WE can alter it through training (and land in a better place in our genetic window) Isoform: Different types of the same protein are available (example. MHC myosin heavy chain fast II b MHC or fast II a MHC or II x MHC) (the "quality of the protein") different isoform can cause different function Genotype: the genetic sequence of DNA that affects the phenotype that we see (the genetic sequence gives a window of potential phenotypes; therefore there are limits on the adaptations and capacities one can have. GENOTYPE UNCHANGABLE WHILE PHENOTYPE IS CHANGEABLE - Muscle gene expression is affected by loading state and hormones o Hormones • Can bind to the outside of a target cell or diffuse through (steroid hormones) and will go into the nucleus where the hormone will interact with hormone response element on a segment of the DNA (gene) that can positively or negatively influence the basal promotor. • The hormone interacts with the hormone response element through the nuclear receptors (HR) to affect transcription • The basal promotor will than affect transcription which will will affect pre mRNA (can lead to degradation), which then affects processing that forms mRNA (can lead to degradation). The mRNA will than affect translation in the cytoplasm, which will affect protein synthesis (proteins can also be degradation) o Loading state →endurance training or strength training • Modify transcription factors, which will positively and negatively influence one another, they will influences other TF and can influences kinases, which phosphorylate. These kinases can shut-off or turn on other TF. Nonetheless, this will change the microenvironment and influence the basal promotor positively or negatively. • NOTE: TF will also positively or negatively affect the binding of TF to their respective receptors on the DNA segment • Activity (loading) changes the levels of certain TF (c-fos, c-jun, REB, MAPK) - The regulation occurs at any level from transcription to post-translational - Transcription factors (TF), which interact with their response elements can affect the promotion of specific genes →this determines which isoform of proteins are being formed

Use well-labelled graphs and point-form descriptions to provide answers to the following questions: a. Illustrate with the use of a graph the oxygen transport cascades at sea level and 4300 m at rest. Show the changes in VO2 moving from atmospheric to alveolar, arterial, and venous content. (Approximate numbers and units are required.) b. Include on the graph the values you would observe during exercise at both sea level and 4300-m altitudes. Label clearly.

NOTE: black line in 4300 m and blue line is sea level; orange line represents exercise PI02- inspired air O2 tension PA02= alveolar O2 tension PaO2=arterial O2 tension PvO2=venous O2 tension - The oxygen cascade is the driving force from the ambient air to the lungs to the blood and eventually the cells - Pulmonary function o During the first 2 weeks of exposure to a high altitude→ventilation increases • Hypoxia is driving force • Bicarbonate is excreted by the kidneys→increase central and peripheral senstivitiy for ventilation o Hypoxic ventilatory response • Important to maintain alveolar and arterial O2, which determines maximal O2 utilization - At alititude the (a-v)O2 will be a lot less because we have less air to give

Explain the potential mechanisms by which proton accumulation may contribute to fatigue

Proton Accumulation (H+): Caused by: Lactic acid build up (free proton) (buildup at lactate inflection point) = happens when production exceeds removal (inflection point) All glycolytic enzymes are weak acids also caused by ATP breakdown Exported into blood from muscle (blood PH decrease) High H+ affects CNS=pain/nausea/discomfort/disorientation=CENTRAL FATIGUE Inhibits O2/Hbcombo in lungs (shifts to right (PH 7.4-7.2) Reduce FFA oxidation cuz reduces HS lipase Can inhibit PFK (slow glycolysis) Can interfere with calcium binding site in Troponin-C (H competes with Ca) Inhibit glycogen phosphorylase Decrease opening of SR Ca+ channels May stimulate pain receptors STILL UNSURE IF THISE CAUSES FATIGUE CAN BE HELPED BY INGESTION OF ANTI ACID (SODIUM BICARBONATE) (take 0.3g/lg of body weight 30 min before anaerobic heavy event)

What factors account for the cardiovascular and strength changes accompanying work in cold environments?

Since you're not excercising u're losing more cold than u wud otherwise Cardiovasc changes= VO2 req at sub max INCREASES!!= Question 9 Peripheral vasoconstriction=increased central blood volume=increased BP &decreased HR(during sub max ex), we don't need to pump as often cuz we have more to pimp( ARTERIOVENOUS Anatomoses close during cold=Not much blood flow (& HEAT) going to hands/feet (periph) (similar to occlusion or BP cuff) Heart=inc BP and Dec HR(during submax ex) Possiblity of arrhythmia and vent fibrillation increase (can cause death) increase Increase input from hypothalamus Increase adrenal epinephran Lower lipid metabolism→reduced BF to adipocytes (even with the increased catecholamines) Release of leptin from adipose tissue→ cuz of increase sympathetic stimulation Increase ventilation at submaximal exercise→increase sympathetic stimulation Strength= Low muscle temp=dec muscle enzyme activity=decrease strength and peak power - Will req. Increased Motor Unit recruitment to make up for reduced output per muscle fiber - Reduce muscle blood flow (periph vasoconstriction to prevent heat loss) - HIGHER RECRUITMENT ALONG WITH LOW BLOOD=Increased lactate production (increase CHO metabolism =Glycogen stores loss) and reduced clearance cuz of low blood flow (EARLY fatigue) - Decrease contractile velocity - Peripheral fibres (forearm) get even colder, lack of ability to contribute anymore, so losing some of muscle (atrophy from lack of use) - We increase the load on other muscles to push to fatigue more rapidly

What evidence would you present to an audience of seniors to convince them that strength training would benefit their daily living?

Strength gain will increase you postural stability and therefore u'll be less likely to fall or fracture you hip. Hip fractures take away your ability to move around and have independence, often hip fracture patients die within a year of their accident. improves postural stability. Your body is as adaptable as young people, you reach amazing % increases in your muscles the same as young peopleIncrease CSA of type 1 (~34%) and 2 fibres (~28%) in VL muscle; this will helps prevent loss of muscle mass and strength. You will feel better (less depression/ have better mental capcity and self efficacy. feel better about themselves You will be less like to suffer from joint problems or bone issues and the problems you have now can become better (PREVENT BONE MINERAL LOSS/ improved Joint health/flexibitly)

What are the cardiovascular responses to exercise in the heat?

THESE effects: Depends on bodies ability to dissipate heat and maintain blood flow to active muscle - Decreased plasma volume (due to increased BP and Sweat(fluid Loss)) - Decreased Central Blood Volume=decreased filling and therefore need for higher HR (HR increase is not viable at very high intensities cuz of TRIAGE!!!!!!) - At high intensity periphery vasoconstriction to maintain BP to Heart and Brain (triage) DEHYDRATION and PREHEATING will effect cardio poorly (less plasma volume to being with) = Decreased VO2 max Sweating response:primary means of heat dissipation and sweat rate is related to exercise intensity rather than environmental temperature 1. If water not replace through sweat will cause a hypohydrated state 2. Moderate level of dehydration will impair CV and temperature regulation—impact performance 3. Note: a fluid loss of 5% of body weight will cause irritability, fatigue, and discomfort. (common if football (padding) and distance running) Ice jackets (delay rise in core temp)help cuz they prevent pre heating=prevent decrease in VO2max

What would be your training recommendations to an elite athlete preparing to compete at moderate altitude? Justify your reasoning. What impact would you expect on sea-level endurance performance? Why?

The athlete needs to go to that moderate altitude weeks before the competition (1-12 weeks of acclimatization would be beneficial) If we keep them up there too long they may get detraining effects because they can't work at the same intensity as sea level. (decreased VO2 max/less Blood Volume/Decreased Buffering capacity/ INCREASED VENT=increased work They do need to do some acclimatization to increase RBC. This hurts sea level endurance performance, because of the possible detraining effect. a. Live high—train low 1. Combine the benefit of sedentary adaptation to altitude with maximal training stimulus near sea level 2. Increased capacity to compete at moderate altitude and sea level 3. Figure 21.6 1. VO2 max and running endurance (performance) improved 1. Maximal steady state VO2 max improved the most for live high and training low when compared to live high and training high and live low and train low 2. 3000m performance improved (elite) 3. Only some subjects were "responders"—significant EP0 production with alititude 4. Either live at 2200-3500 m and drive down every day to train (<1200 m) 1. This altitude found toincrease EPO count and stimulate RBC production, but to not cause AMS symptoms in athletes 1. While training at sea level will prevent any detraining effect due to increase relative work rates 2. much higher will effect illness, nutritional intake, ability to train so go to moderate altitude to live 5. can also sleep in hypoxic tent with reduced oxygen tension(14% O2-PI02 106 mmHg) →changes % O2 in air without changing barometric pressure 1. stimulates adaptations while you sleep

What is the effect of hypoxia on work capacity before and after chronic exposure to hypoxia?

a. Athletes can benefit from 1-12 weeks of acclimatization b. Problem: reduced absolute training intensity at altitude-even if same relative % 1. Cannot train as hard—detraining effect→despite having an increase in all the physiological variables 2. Further—do not see improvements in sea level performance (reduction) 3. Reduced blood volume, buffering capacity, increase ventilation (more work) c. Weight loss and muscles will atrophy on average 100-200 g/day due to dehydration, energy deficit, increased activity and BMR 1. Recommend a high CHO diet that is greater than 60% 1. This is because they have a higher yield of ATP/O2 2. CHO also have very limited storage 1. Hypoglycaemia and liver glycogen depletion common at altitude 1. Reduced with high CHO diet 2. Fat and protein 1. Increase fat catabolism at altitude if diet is inadequate 2. Gluconeogenesis—loss of muscle mass also occurs with low CHO intake 3. Working muscles shown to prefer CHO at altitude 1. Use of protein for gluconeogenesis has detrimental impact on long term exercise /work potential d. Decrease epinephrine (nor-epinephrine stays high), this decrease will decrease lactate producuction (LACTATE PARADOX= increase in lactate prod at altitude but VO2 max doesn't change, Lactate threshold doesn't correspond to VO2max) 1. Reduces glycogen mobilization→less lactate as a by product 2. Working muscle oxidizes more of its own lactate—increase independence on blood glucose Hypoxia - low levels of O2 (low tension of O2). Oxygen transport capacity (ability to get it to the working muscles) decreases with increasing altitude, even with compensations from acute exposure. - Pulmonary Function is the rate limiter at altitude, even after acclimatization, so any given absolute work rate will be at a higher % of their VO2 max when at altitude, before and after acclimatization. This affects our work capacity. - we have less oxygen and as a result ventilation will increase for the first 2 weeks at altitude→we will see changes with acclimitization→hypoxia is the driving force and kidney excretion of HCO2 will make the central and peripheral sensitivity for ventilation - We will get more of a detraining effect at alititude because we cant work at same absolute work even if same relative % of our VO2 max—compared to sea level—thus we will hit fatigue earlier if we are working at the same work rate o According to figure 21-6 we will see an increase in VO2 max with living high and training high but not as much of an increase as live high-train low Before chronic adaptation - we can see illness, decreased nutritional intake →can affect metabolism and energy provision. - A reduced diet causes breaking down body tissues for energy supply, protein (make sure you're getting lots of carbs so you're not breaking down proteins while hiking, keep and build muscle mass, use protein to make RBCs, Hb, and Hct), and iron (each Hb molecule requires iron) intake. - Running out of energy will cause early fatigue, affecting our work capacity Unacclimatized: higher epinephrine content and more lactate appears, causing fatigue. Acclimatization: catecholamines decrease and working muscle may oxidize more of its own lactate (intracellular lactate shuttle so less of lactate out into blood so don't measure it) Before chronic adaptation: hypoglycemia and liver glycogen depletion are common. Carbohydrates are the preferred fuel - higher yield of ATP/mol of O2, more efficient. Depletion will affect work ability. Fatigue will occur when glycogen has been depleted, affecting work capacity. Endurance capacity increases with chronic exposure compared to acute (recall we separated endurance ability and VO2 max). Adaptation to chronic hypoxia exposureimproves our limiting O2 by increasing RBC count, increasing EPO production with altitude. With acclimatization we see improved O2 transport with increased tissue myoglobin, increased skeletal muscle and pulmonary vascularity, increases bp, and decreased plasma volume, increased Hb, RBC, and hematocrit []s. Max strength is unaffected by altitude, but capacity for repeated contractions becomes impaired.