Metabolism Metabolism ▪ catabolism + anabolism ▪ intake and distribution of nutrients, water and oxygen, their biotransformation, removal of waste metabolites from the organism ▪ gain of energy from chemical bonds in food, its conversion to ATP ▪ energy is needed for: muscle contraction Na+/K+ transport proteosynthesis Ca2+ export ▪ at the organ level: muscle heart kidney Metabolism Energy store ▪ glycogen (storage saccharide) – approx. 500 g (400 g muscles and 100 g liver); energy for app. 30-90 min of activity ▪ glucose – around 20 g in blood (100 kcal); energy mainly for brain and blood cells ▪ fat – app. 112.000 kcal, it means around 80 % of stores in organism ▪ proteins – app. 25.000 kcal, normally not used to produce energy Units: calorie (cal); joule (J) cal = 4,18 J J = 0,239 cal kcal = 1000 cal = 4,18 kJ Control of metabolism ▪ energy demand and consumption ▪ endocrine hypothalamic-pituitary-thyroid axis ▪ thyrotropin-releasing hormone (TRH) from hypothalamus ▪ stimulation of the anterior pituitary to produce thyroid-stimulating hormone (TSH) ▪ stimulates the thyroid to produce thyroid hormones triiodothyronine (T3) and thyroxine (T4) ▪ thyroid hormones increase the basal metabolic rate ▪ negative feedback loop in the axis Measurement of metabolism Direct calorimetry ▪ Antoine-Laurent de Lavoisier (1743-1794) ▪ relationship between the level of metabolism and the heat production ▪ respiratory gas exchange is the combustion Measurement of metabolism Indirect calorimetry (respirometry) ▪ August Krogh (1874-1949), Barcroft ▪ relationship of O2 consumption, CO2 release and level of metabolism ▪ energy equivalent (EE) = amount of energy released from substrate which is burned using 1 liter of O2 (on average 20,2 kJ) ▪ respiratory coefficient (RQ) depends on the specific-dynamic effect of the nutrients; determinates the combusted nutrients ▪ C6H12O6 + 6O2 → 6CO2 + 6H2O ▪ pure saccharides (RQ = 1), proteins (RQ = 0,8), lipids (RQ = 0,7) ▪ on average RQ = 0,85 RQ = CO2 O2 Basal a total metabolism ▪ basal M = lowest amount of energy necessary to provide basic functions of the organism • absolute mental and physical calm • termoneutral zone (naked 27 °C, dressed 20 °C) • restricted food income (last meal 12 hours before measurement, proteins restricted 3 days before measurement) ▪ men 171 kJ/h/m2, women 151 kJ/h/m2 ▪ total M = BM + activity + effect of temperature Surface hypothesis ▪ Max Rubner (1854 - 1932) ▪ the metabolic rate of birds and mammals that maintain a steady body temperature is roughly proportional to their body surface area Calculation of basal metabolism rate (BMR) ▪ Harris and Benedict, 1918 BMR (women) = 665,51 + (9,56 × weight in kg) + (1,85 × height in cm) − (4,68 × age in years) kcal/day (convert to kJ/day) BMR (men) = 66,47 + (13,75 × weight in kg) + (5,00 × height in cm) − (6,76 × age in years) kcal/day (convert to kJ/day) 1 kcal = 1000 cal = 4,18 kJ Example: man (age 29; weight 66 kg; height 171 cm): 1633 kcal/day = 6826 kJ/day ▪ spirometry according to Krogh ▪ natrokalcid: NaOH (absorbs CO2) + CaCl2 (absorbs H2O) ▪ BMR: men 171 kJ/hr/m2, women 151 kJ/hr/m2 V5 = x (l O2 per 5 min) V1 = x / 5 (l O2/min) BM1 = V1 x EE (kJ/min) BM = … (kJ/day, kcal/day) BM = BM1 x 60 / S (kJ/h/m2) BM = BM1 x 60 / m (kJ/h/kg) Practice: Human metabolism time l O2 3,0 2,5 2,0 1,5 1,0 0,5 0 5 min Practice: Measurement of insect metabolism ▪ larvae of Galleria mellonella, Bombyx mori, Tenebrio molitor or Zophobas morio 1. Weight the model organisms … m (g) 2. Prepare chambre for measurement 3. Measure 4 x 3 min oxygen consumption (D O2) 4. Calculate mean of oxygen cons. D O2 (ml / 3 min / m g) 5. Convert to liter and use EE to multiply (kJ / 3 min / m g) 6. Convert per hour and gram of weight (kJ/hod/g) 7. Compare to human (kg vs. g!) Time (min) DO2 (ml) 3 6 9 12 Mean x ml / 3 min Breathing and pulmonary ventilation Respiratory system ▪ respiratory exchange ▪ oxygen intake – diffusion, gill, trachea, skin, lungs etc. ▪ lungs freely in chest ▪ stretched by underpressure ▪ pleura visceralis, pleura parietalis ▪ pneumothorax Respiratory system ▪ alveolo-capillary exchange (membrane ~ 1μm), diffusion ▪ pulmonary alveoli Control of pulmonary ventilation ▪ air is composed of: 21 % O2; 78 % N; 1 % Ar; 0,03 % CO2 ▪ hypoxia vs. density of vascular system ▪ respiratory center: medulla oblongata (inspirium/exspirium) ▪ chemoreceptors - blood pH (cervical artery, aortic bodies) ▪ baroreceptors - lung expansion (↑ pressure activates exhalation) ▪ proprioreceptors - muscles and tendons (activity intensifies breathing) ▪ thermoreceptors (heat intensifies breathing) Respiratory disorders Lung cancer Emphysema Cystic fibrosis Pneumothorax Asthma chronic obstructive pulmonary disease Mechanism of pulmonary ventilation Inspirium ▪ active ▪ diaphragm, muscles of rib cage and other muscles ▪ forceful inhalation Exspirium ▪ passive ▪ active chest compression ▪ frequency of breath: human 16-20 breaths/min children 26 breaths/min, newborns 44 breaths/min horse 8-16 breaths/min, mouse up to 200 breaths/min ▪ thoracic (female) vs. abdominal (men) Krogh/Hutchinson respirometer John Hutchinson (1811-1861) August Krogh (1874-1949) Vital capacity (VC) (ml) Vital capacity (VC) Inspiratory reserve volume (IRV) 2500 ml Tital volume (TV) 500 ml Exspiratory reserve volume (ERV) 1000 ml Residual volume (RV) 800-1700 ml (collapse + minimal) Factors: ▪ age ▪ sex ▪ skin area ▪ fitness ▪ pathologies ▪ etc. Practice: Forced vital capacity (FVC) ▪ the determination of the vital capacity from a maximally forced expiratory effort ▪ Hutchinson‘s respirometer ▪ normal VC: Women ~3100 ml Men ~4600 ml ▪ normal VC: Women 2000 ml/m2 Men 2500 ml/m2 ▪ theoretical VC (European population): ♀ Women: 5,2 x height (m) – 0,018 x age – 4,36 (+/- 0,42) ♂ Men: 5,2 x height (m) – 0,022 x age – 3,6 (+/- 0,58) Practice: Dynamic test (FEV1) ▪ volume that has been exhaled at the end of the first second of forced expiration ▪ Krogh‘s respirometr; normally > 85 % ▪ restrictive pulmonary diseases – lower vital capacity (< 75 %) ▪ obstructive pulmonary diseases – lower FEV1, normal VC -20 0 20 40 60 80 100 120 1 2 3 4 5 6 7 sec1sec VC total VC sec Vitalcapacity(%) Dynamic test of pulmonary ventilation ▪ normal ▪ fibrosis, scars, deformities (restrictive) ▪ mucus production, inflammation, bronchoconstriction, asthma (obstructive) 0 10 20 30 40 50 60 70 80 90 100 1 2 3 4 5 6 7 8 9 10 11 12 13 14 sec Vitalcapacity(%)