FIG 23.2 Cellular respiration, which results in the release of the energy of the terminal phosphate bond of adenosine triphosphate to fuel the contractile and related demands of the working skeletal muscle ATP, Adenosine triphosphate (From Astrand P, Rodahl K The Muscle and Its Contraction Textbook of Work Physiology, Physiological Bases of Exercise 3rd ed McGraw-Hill; 1986:12–53.) Anaerobic and aerobic metabolic activities use glucose, which is metabolized to pyruvate Pyruvate then has two possible fates It may be converted into lactic acid and excreted into the bloodstream, where it is buffered by sodium bicarbonate converting it to lactate This reaction results in the production of carbon dioxide and water, along with small amounts of adenosine triphosphate, and the former are excreted in the lungs The lactate molecule is taken up by the liver for resynthesis to glucose and glycogen, which can then be used again for energy production The other fate of pyruvate is aerobic metabolism Pyruvate is converted into acetyl-coenzyme A and transported into the mitochondria, where it enters the Krebs cycle, again producing carbon dioxide and water Adenosine triphosphate is produced in large quantities via the electron transport chain, with oxygen functioning as the terminal electron acceptor Unlike anaerobic metabolism, fats and carbohydrates can undergo aerobic metabolism Fats enter aerobic metabolism at the level of the Krebs cycle and do not undergo anaerobic metabolism.4,5 During any activity, the availability and use of substrates, primarily fats or carbohydrates, will vary depending upon the type, intensity, and duration of activity Fats are more reduced than carbohydrates, requiring more oxygen for complete oxidation compared with carbohydrates on a mole-for-mole basis.4 The ratio of production of carbon dioxide to consumption of oxygen, abbreviated to VCO/VO, is called the ratio of respiratory exchange or, if in a steady state, the respiratory quotient In a state of high use of fat, the ratio is approximately 0.7 Conversely, during pure carbohydrate metabolism, the ratio is 1.0, reflecting the lower amount of oxygen needed to oxidize carbohydrates The stores of glycogen in the adult body are seldom more than approximately 1500 Kcal Therefore some use of fat is almost always required As a result, the resting ratio of respiratory exchange, even in the well-fed state, will usually range from 0.85 to 0.9 During a typical graded maximal exercise test, the work rate is gradually increased over the course of approximately 10 to 15 minutes, as explained in our subsequent sections concerning exercise protocols Production of adenosine triphosphate will need to increase as mechanical work increases, and at low levels of work this increase is met predominately by increased aerobic metabolism As work rate increases, consumption of oxygen increases in a linear fashion (Fig 23.3) Near peak work rates, oxygen consumption will tend to plateau, as maximal consumption is achieved This phenomenon is often absent in children.4,6,7 FIG 23.3 Relationship between consumption of oxygen (VO2) and rate of work during progressive exercise in a healthy and well-conditioned adolescent Note that with the onset of exercise there is an essentially linear relationship between these two features until near the peak of exercise when VO2 plateaus despite the continued rise in rate of work As consumption of oxygen increases in response to increased work rate, there is a gradual rise in the ratio of respiratory exchange The reason for this rise is twofold First, there is a gradual shift in use of carbohydrates compared with fats This shift allows for more efficient use of oxygen because the yield of adenosine triphosphate per liter of oxygen is greater with carbohydrates compared with fats Secondly, the rise in the ratio occurs as a result of increased levels of lactic acid in the blood At approximately 50% to 60% of the maximal consumption of oxygen, levels of lactic acid begin to rise in the serum This point is known as the lactate threshold The onset of anaerobic metabolism by the exercising muscles is responsible for this production of lactic acid The etiology of the lactate threshold appears to be the limited delivery of oxygen to the exercising muscles.8 The oxygen tension in the exercising muscle capillary bed must remain at a level that will allow the diffusion of dissolved oxygen to the exercising muscle's mitochondria At sea level, barometric pressure and a normal arterial hemoglobin content, approximately 6 L of blood must be delivered to the exercising muscles for each liter of oxygen used in aerobic metabolism, to maintain this critical capillary oxygen tension throughout the course of the capillary bed.9 Above the threshold, levels of lactic acid rise exponentially as work rate increases, necessitating increased buffering by sodium bicarbonate to maintain blood pH homeostasis The by-product of the buffering process, carbon dioxide,