Interaction between hypometabolism and acid–base balance

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This review discusses the changes in acid–base balance that are produced during hypometabolism and the negative feedback role they play in maintaining the hypometabolic state. In prolonged hypometabolism, air-breathing animals consume internal stores of fat, protein, and carbohydrate, while glycogen is the primary fuel supporting anaerobic hypometabolism. Because the excretory processes are greatly reduced, the accumulation of waste products must be dealt with internally. Mitigating strategies to minimise acid–base disturbance are seen in higher buffer capacities, an acid shift in the pH optima of key enzymes, and the use of metabolic pathways that result in a reduction of net H+ production. In some hibernating animals, gut bacteria may play an important role in preventing [Formula: see text] accumulation. However, the compensatory mechanisms are only partially successful, and substantial alterations in acid–base status and related strong ion changes are common. Changes in intracellular pH have wide metabolic effects but the acid–base and ionic status of the cell is dependent on its energy expenditure. The most vulnerable tissue to reduced metabolism is the brain. The turtle brain can greatly lessen its energy requirements by reducing activity; this is achieved by (i) depression of synaptic transmission, (ii) membrane hyperpolarisation through opening of Cl− channels resulting from release of γ-aminobutyric acid, and (iii) slowing transmembrane ion flux by the selective closure of ion channels. CO2 retention is common in hypometabolic animals. Increased levels of CO2 and H+ and decreased [Formula: see text] can directly cause metabolic depression via a variety of mechanisms, as well as a reduction in neural tissue activity. It is concluded that the hypometabolic state represents a very general condition of temporarily reduced energy expenditure which embraces aestivation, hibernation, torpor, and sleep, and that the common phenomena of CO2 accumulation and consequent changes in acid–base balance play a role in the coordinated reductions in energy expenditure and energy cost.