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The energy consumption of the human body increases during physical exercise, especially in the active muscle cells. The synthesis of ATP, the unique direct energy source in skeletal muscles, depends on oxygen availability in skeletal muscle cells and can be a product of aerobic or anaerobic processes. To meet the increased demand for oxygen during incremental submaximal exercise, our body adapts locally with enhanced perfusion of working muscles and with increased cardiac output and ventilation as a whole. At a working rate called anaerobic threshold, there is not enough oxygen to satisfy energy demands. Therefore, anaerobic energy production is switched on, leading to H+ and lactate accumulation in active muscle cells. Both anaerobic metabolic products leave muscle cells by passing through monocarboxylate transporters in sarcolemma. H+ions are buffered with bicarbonate in the blood until buffer capacity suffices. Ventilation increases to exhale additional oxygen dioxide produced. When blood H+ concentration increases, the ventilation is further stimulated by H+ sensitive central chemoreceptors. The role of lactate during physical exercise is very important. It is a good marker for cell metabolic conditions indicating the onset of anaerobic metabolism at lactate threshold and the highest anaerobic turnover, where maximal steady-state blood lactate concentration is maintained. It prevents pyruvate accumulation in muscle cells and serves as a useful aerobic fuel for oxidative muscular contraction. Metabolic changes during physical exercise are coupled with increased ventilation reflected by the ventilation equivalent ratio defined as the volume of ventilated air per one liter of consumed oxygen. Ventilation equivalent has the lowest value during light workout (15–20 l air/l oxygen), increases at ventilation threshold and escalates at respiratory compensation point (30–45 l air/l oxygen). Ventilation threshold correlates with lactate threshold and respiratory compensation point with maximal steady-state blood lactate concentration. Metabolic and ventilation changes are related to cardiovascular adjustments during physical exercise.