Department of Physiology, Faculty of Medicine, Masaryk University1 Energetic metabolism Physiology II lecture (aZLFY0422p) Tibor Stračina Physiology II lecture (aZLFY0422p)2 Energetic metabolism ̶ Energy input (external an internal sources) ̶ Energy output ̶ Energy stored ̶ INPUT = OUTPUT + STORAGE ENERGY INPUT ENERGY OUTPUT STORAGE ENERGY INPUT ENERGIE OUTPUT STORAGE Physiology II lecture (aZLFY0422p)3 Energy input ̶ Basic substrates: carbohydrates, fats a proteins ̶ Energy is obtained by burning (oxidizing) substrates ̶ carbohydrates 4,1 kcal/g ̶ fats 9,3 kcal/g ̶ proteins 5,3 kcal/g (in the body 4,1 kcal/g) ̶ Source of substrates: food intake or mobilization of reserves Physiology II lecture (aZLFY0422p)4 Nutrient burning GLYCOLYSIS b-OXIDATION carbohydrate C6H6O6 (2)pyruvate (2)acetyl-CoA(n/2) 2ATP 4xATP 4H 4H Each acetyl-CoA Citrate cycle 8H Fatty acid CnH2nO2 ATP 2(n-2)H 2(n-2)H O2 + ADP Oxidative phosphorylation ATPH2O 2 CO2 GTP protein AA Physiology II lecture (aZLFY0422p)5 Energy output ̶ Basal metabolism – energy expenditure to maintain homeostasis under basal conditions (vital function) – ~75% of AEE in a person sitting at rest ̶ Specific dynamic effect of food – a small increase in energy expenditure after eating– ~7% of AEE in a person sitting at rest ̶ Thermoregulation ̶ Spontaneous motoric activity– ~18% of AEE in a person sitting at rest ̶ Physical work (exercise) Physiology II lecture (aZLFY0422p)6 Energy storage and transfers ̶ Irregular energy intake and output – the need for energy storage ̶ Ready-to-use stock - macroergic compounds ̶ ATP ̶ creatin phosphate ̶ GTP, CTP, UTP, ITP ̶ Long-term storage – stock substrates ̶ Fat, proteins, glycogen Physiology II lecture (aZLFY0422p)7 Adenosine trisphophate (ATP) ̶ universal macroergic compound Synthetis ̶ circa 63 kg/day (128 mol/day) ̶ oxidative phosphorylation ̶ glykolysis – for short-term production only, production of lactate Use ̶ macroergic bond splitting – efficiency is not 100%, heat release Physiology II lecture (aZLFY0422p)8 Storage substrates ̶ Triacylglycerols in fat tissue (75% of stores) – up to 2 months ̶ Source: FA from food and esterification with α-glycerol phosphate or synthesis of FA from acetyl-CoA from glycolysis (conversion of sugars into a more efficient energy store = fat) ̶ Proteins in skeletal muscles and blood plasma (25% of stores) ̶ Possible conversion to sugars (glukoneogenesis; stimulated by glucocorticoids) ̶ Blood plasma proteins – quickly usable; leads to hypoproteinemia, drop of specific immunity ̶ Mobilization of muscle proteins leads to sarcopenia ̶ Carbohydrates in form of glycogen (less than 1% of stores) ̶ Important for the CNS and covering energy demands during short-term physical work ̶ Glycogen stored in the liver (about 25%) and in the muscles (about 75%) ̶ Liver glycogen - glycogenolysis - release of Glc into the blood ̶ Muscle glycogen - use only in muscles (glucose-6-phosphatase is missing) Physiology II lecture (aZLFY0422p)9 Energy transfers between organs ̶ Only in the form of substrates (glucose, FA, AA, lactate, ketons, ...) ̶ Any transfer of substrates consumes some energy (synthesis and splitting of stock substrates, transports, ...) Fat tissue Muscles Liver Triacylglycerols Free FA FA CO2 Muscle work Lactate Lactate Pyruvate Glucose Glucose ATP H+ Physiology II lecture (aZLFY0422p)10 Measurement of energy expenditure ̶ Direct calorimetry ̶ Indirect calorimetry (PRACTICE!!!) ̶ Consumption of O2 – energetic equivalent of oxygen (amount of energy released when consuming 1 liter of O2) carbohydrate: 21,15 kJ/l fat: 19,6 kJ/l protein: 19,65 kJ/l mixed diet: 20,1 kJ/l ̶ Consumption of O2 + production of CO2 – respiratory quotient (RQ = VCO2 / VO2 ) carbohydrate: RQ = 1 fat: RQ = 0,7 protein: RQ = 0,8 – 0,9 Department of Physiology, Faculty of Medicine, Masaryk University11 Physiology of Exercise Physiology II lecture (aZLFY0422p) Tibor Stračina Physiology II lecture (aZLFY0422p)12 Work (physical activity, exercise) Source: www.freepik.com. Photos created by freepik and standret Physiology II lecture (aZLFY0422p)13 Skeletal muscle ̶ Contraction: isometric (static work) vs. isotonic (dynamic work) ̶ Blood flow depends on muscle tension ̶ Metabolic autoregulation: ↓pO2; ↑pCO2; ↓pH; ↑K+; ↑local temperature ̶ Metabolism: aerobic vs. anaerobic ̶ Muscle spindles – muscle tension – afferentation of exercise pressor reflex Physiology II lecture (aZLFY0422p)14 Skeletal muscle metabolism Adopted from: D.U.Silverthorn: Human Physiology (An Integrated Approach) Physiology II lecture (aZLFY0422p)15 Reaction of the body to exercise ̶ Sympathetic NS (ergotropic system) ̶ Cardiovascular changes ̶ Respiratory changes ̶ Metabolic changes ̶ HOMEOSTASIS Physiology II lecture (aZLFY0422p)16 Anticipation of exercise ̶ Reaction of the body (cardiovascular system) ̶ Prepare the body for the increased metabolism of the exercising skeletal muscles ̶ Same as the early response to exercise ̶ Resembling fight-or-flight reaction Physiology II lecture (aZLFY0422p)17 Cardiovascular response to exercise ̶ Increased cardiac output ̶ Vasoconstriction in inactive skeletal muscles, the GIT, skin, (kidneys) ̶ Vasodilation in active muscles (metabolic autoregulation) ̶ Increased venous return ̶ Histamine release ̶ Epinephrine release (adrenal medulla) ̶ Thermoregulation Physiology II lecture (aZLFY0422p)18 Increase of cardiac output. Cardiac reserve ̶ CO = SV x HR (SNS: positive inotropic and chronotropic effect) ̶ Cardiac reserve = maximal CO / resting CO (4 – 7) ̶ Coronary reserve = maximal CF / resting CF (~3.5) ̶ Chronotropic reserve = maximal HR / resting HR (3 – 5) ̶ Volume reserve = maximal SV / resting SV (~1.5) CO – cardiac output; CF – coronary flow; HR – heart rate; SV – stroke volume Physiology II lecture (aZLFY0422p)19 Changes of arterial blood pressure PARAMETER AT REST DURING EXERCISE INCREASE (x) Cardiac output [L/min] 5 – 6 25 (35) 4 – 5 (7) cardiac reserve Heart rate [1/min] (45) 60-90 190 – 200 (220) age-dependent 3 – 5 chronotropic reserve Stroke volume [mL] 75 115 ~1.5 volume reserve Systolic BP [mmHg] 120 static work ↑ dynamic work ↑↑ Diastolic BP [mmHg] 70 static work ↑↑↑ dynamic work ─ / ↓ Mean arterial P (MAP) [mmHg] ~90 static work ↑ dynamic work ─ / ↑ Muscle persufion [mL/min/100g] 2 – 4 60 – 120 (180) static vs. dynamic work 30 (10% COmax) Physiology II lecture (aZLFY0422p)20 Respiratory response to exercise ̶ Respiratory centre - ↑ ventilation ̶ chemoreceptors: ↑ pCO2 + ↓ pH ̶ proprioceptors in lungs ̶ Sympathetic stimulation (stress – anticipation) Physiology II lecture (aZLFY0422p)21 Respiratory response to exercise PARAMETER AT REST DURING EXERCISE INCREASE (x) Ventilation [L/min] 6 – 12 90 – 120 15 – 20 respiratory reserve Breathing frequency [1/min] 12 – 16 40 – 60 4 – 5 Tidal volume (VT) [mL] 0.5 – 0.75 ~2 3 – 4 Pulmonary artery blood flow [mL/min] 5 – 6 25 – 35 4 – 6 O2 uptake (VO2) [mL/min)] 250 – 300 ~3000 10 – 12 (25) CO2 production [mL/min] ~200 ~8000 ~40 Physiology II lecture (aZLFY0422p)22 Oxygen uptake by lungs ̶ Spiroergometry ̶ Resting VO2: ~3.6 mL O2 / (min x kg) ̶ VO2 max – objective index for aerobic power ̶ untrained middle age person: 30 – 40 mL O2 / (min x kg) ̶ elite endurance athletes: 80 – 90 mL O2 / (min x kg) ̶ HF / COPD patients: 10 – 20 mL O2 / (min x kg) Adopted from: https://studentconsult.inkling.com/read/boron- medical-physiology-3e/chapter-60/figure-60-6 Physiology II lecture (aZLFY0422p)23 Determinants of VO2 max 1. Uptake of O2 by the lungs ̶ pulmonary ventilation 2. O2 delivery to the muscles ̶ blood flow (pressure gradient – cardiac output x resistence) ̶ haemoglobin concentration 3. Extraction of O2 from blood by muscle ̶ pO2 gradient: blood-mitochondria Physiology II lecture (aZLFY0422p)24 Oxygen consumption during exercise ̶ Oxygen debt Adopted from: D.U.Silverthorn: Human Physiology (An Integrated Approach) Physiology II lecture (aZLFY0422p)25 Blood gases during exercise Adopted from: D.U.Silverthorn: Human Physiology (An Integrated Approach) Physiology II lecture (aZLFY0422p)26 Energy substrate used by skeletal muscle during exercise ̶ Low-intensity e.: fats ̶ High-intensity e.: glucose Adopted from: D.U.Silverthorn: Human Physiology (An Integrated Approach) Physiology II lecture (aZLFY0422p)27 Energy substrate use – aerobic vs. anaerobic Adopted from: D.U.Silverthorn: Human Physiology (An Integrated Approach) Physiology II lecture (aZLFY0422p)28 Testing of fitness ̶ Spiroergometry ̶ Standardised workload ̶ accurate: in W/kg ̶ comparative (simple, inaccurate): in MET ̶ metabolic equivalent (actual MR / resting MR) ̶ 1 MET = uptake of 3.5 ml O2/kg.min ≈ 4.31 kJ/kg.h ̶ sleeping ≈ 0.9 MET; slow walking ≈ 3-4 MET; fast running ≈ 16 MET Physiology II lecture (aZLFY0422p)29 Indexes of fitness ̶ W170 [W/kg] ̶ VO2 max [mL O2 / (min x kg)] ̶ Aerobic / anaerobic threshold ̶ Fatigue ̶ Training ̶ Adaptation to exercise Department of Physiology, Faculty of Medicine, Masaryk University30 Thermoregulation Physiology II lecture (aZLFY0422p) Tibor Stračina Physiology II lecture (aZLFY0422p)31 Body temperature – homeostatic parameter 45 40 35 30 25 Heat stroke Hard exercise, fever Normal body temperature (36,3 – 37,1°C) Loss of consciousness Muscle failure, cardiac fibrillation HYPER- THERMIA HYPO- THERMIA Physiology II lecture (aZLFY0422p)32 Body core vs. shell ̶ homeotherms vs. poikilotherms ̶ Body core temperature – regulated within certain (narrow) range ̶ Skin temperature (shell) – more variable (ambient t., core body t.) Adopted from: K.S. Saladin, Anatomy & Physiology—The Unity of Form and Function, 8th ed. (McGraw-Hill, 2018) Physiology II lecture (aZLFY0422p)33 Variations of body core temperature ̶ Circadian rhythm ̶ Circamensal rhythm (women between puberty and menopause) ̶ Seasonal variations (circannul rhythm) ̶ Ageing Physiology II lecture (aZLFY0422p)34 Variations of body core temperature Physiology II lecture (aZLFY0422p)35 A fine balance of body core temperature HEAT PRODUCTION HEAT INTAKE HEAT OUTPUT HEAT LOSS Physiology II lecture (aZLFY0422p)36 Heat vs. temperature ̶ Heat [J] – energy transfered to or from the system; measure of the internal energy state ̶ Temperature [K, °C, °F] – a measure of heat content; mean kinetic energy of the particles (molecules, ions) Physiology II lecture (aZLFY0422p)37 Transfer of heat within the body ̶ primarily by CONVECTION ̶ medium = blood ̶ minor amount by CONDUCTION ̶ direct contact of organs/tissues Physiology II lecture (aZLFY0422p)38 Heat production ̶ Metabolism: metabolic rate ≈ heat production ̶ Physical activity (active muscle contraction) – rest vs. exercise ̶ Postprandial thermogenesis (food intake) ̶ Shivering thermogenesis ̶ Non-shivering thermogenesis (brown adipose tissue) Physiology II lecture (aZLFY0422p)39 Heat intake and loss ̶ passive processes ̶ RADIATION ̶ CONVECTION ̶ CONDUCTION ̶ skin-environment temperature gradient Physiology II lecture (aZLFY0422p)40 Heat output (active loss) ̶ EVAPORATION ̶ sensible perspiration = sweat production (1 L of evaporated s. = 2 428 kJ) ̶ Insensible perspiration = diffusion of water through skin and mucosae ̶ from the skin to the environment ̶ (RADIATION) ̶ (CONDUCTION) ̶ (CONVECTION) Physiology II lecture (aZLFY0422p)41 Thermoregulation ̶ All processes involved in keeping the body core temperature within the range ̶ Thermoregulatory behaviour ̶ Social thermoregulation Physiology II lecture (aZLFY0422p)42 Afferentation ̶ Central thermoreceptors – deep brain temperature ̶ temperature-sensitive neurons in anterior preoptic hypothalamus ̶ Peripheral thermoreceptors – skin temperature ̶ TRP channels Adopted from:: https://doi.org/10.1016/bs.pmbts.2015.01.002 Physiology II lecture (aZLFY0422p)43 Thermoregulatory centre ̶ anterior preoptic HYPOTHALAMUS ̶ integration of afferent information ̶ modifying the efferent pathways (vegetative, somatic) to the thermal effectors ̶ „set-point“ vs. threshold temperature for the effector(s) Physiology II lecture (aZLFY0422p)44 Thermal effectors ̶ Behaviour ̶ Cutaneous circulation ̶ Sweat glands ̶ Skeletal muscles (shivering) ̶ Horripilation ̶ Brown adipose tissue (nonshivering thermogenesis) Physiology II lecture (aZLFY0422p)45 Cold-induced thermoregulatory mechanisms ̶ Decrease of heat loss ̶ Behaviour: Decrease of body surface, taking warm clothes ̶ Vasoconstriction in the skin. Horripilation ̶ Inhibition of sweating ̶ Increase of heat production ̶ Skeletal muscles: Intentional movements (behaviour). Shivering ̶ Nonshivering thermogenesis (brown adipose tissue, NA, β3R, UCP1) ̶ Hunger (increas of food intake) Physiology II lecture (aZLFY0422p)46 Warm-induced thermoregulatory mechanisms ̶ Increase of heat loss/output ̶ Skin vasodilatation ̶ Increase of sweating (evaporation) ̶ Increase of ventilation ̶ Decrease of heat production/intake ̶ Behaviour: Moving out of the sun, taking light clothes. Inactiveness (decrease of intentional movements), apathy ̶ Loss of appetite Department of Physiology, Faculty of Medicine, Masaryk University47 Adaptation Physiology II lecture (aZLFY0422p) Tibor Stračina Physiology II lecture (aZLFY0422p)48 Adaptation ̶ Long-term functional and/or structural change as a response to long-term or repeated change (on certain level) of the environment ̶ Leads to decrease of energetic demand for keeping homeostasis in changed conditions ̶ Evolution (fixed adaptation) Physiology II lecture (aZLFY0422p)49 Adaptation: starting up Stimulus ̶ Suprathreshold change of external and/or internal environment ̶ It works long-term or repeatedly Physiology II lecture (aZLFY0422p)50 Adaptation to exercise: Strength vs. Endurance training Source: www.freepik.com - photo created by gpointstudio Source: www.freepik.com - photo created by alexeyzhilkin Physiology II lecture (aZLFY0422p)51 Adaptation to exercise ̶ Skeletal muscles ̶ Hypertrophy, vascularization ̶ Cardiovascular system ̶ Heart adaptation (concentric hypertrophy vs. athletic heart) ̶ Increase in RBC and heamoglobin concentration ̶ Respiratory system ̶ Increase in VC (if possible), increase in maximal respiartion (increase in respiratory reserve), more effective diffusion on alveolo-capillar membrane ̶ Metabolism Physiology II lecture (aZLFY0422p)52 Athletic heart ̶ Adaptation to endurance training ̶ ↑ LVEDV - ↑ SV - (baroreflex) ↓ HR ̶ ~ CO ̶ ↑ chronotropic reserve = ↑ cardiac reserve Source: https://assets.beta.meta.org/discover/thematic-feed/83-athletic-heart-syndrome.jpg Physiology II lecture (aZLFY0422p)53 Cardiac reserve in trained and untrained 0 10 20 30 40 0 1 2 3 4 5 CO[L/min] External power output [W/kg] trained (athletic heart) untrained (physiological response) heart failure Physiology II lecture (aZLFY0422p)54 Oxygen uptake in trained and untrained Source: https://studentconsult.inkling.com/r ead/boron-medical-physiology- 3e/chapter-60/figure-60-6 Physiology II lecture (aZLFY0422p)55 Determinants of VO2 max 1. Uptake of O2 by the lungs ̶ pulmonary ventilation 2. O2 delivery to the muscles ̶ blood flow (pressure gradient – cardiac output x resistence) ̶ haemoglobin concentration 3. Extraction of O2 from blood by muscle ̶ pO2 gradient: blood-mitochondria Physiology II lecture (aZLFY0422p)56 Adaptation to extreme temperatures Source: www.freepik.com Physiology II lecture (aZLFY0422p)57 Adaptation to cold environment ̶ Strategy: reduction of heat loss (+ increase of heat production) ̶ Increase in appetite ̶ An increase in the subcutaneous fat layer ̶ Re-set of the thermoregulation center ̶ Lowering the temperature to activate shivering thermogenesis Physiology II lecture (aZLFY0422p)58 Adaptation to hot environment ̶ Strategy: increase heat loss + decrease heat production ̶ Decreased appetite (appetite) ̶ Adaptation of sweating ̶ Dependent on environmental humidity; reduction of sweat production, reduction of ion concentration ̶ Re-set of the thermoregulation center ̶ Increase in temperature to activate sweating Physiology II lecture (aZLFY0422p)59 The presentation is copyrighted work created by employees of Masaryk University. Any unauthorised reproduction or distribution of the presentation or individual slides is against the law.