Because most cells in the body are electronegative to the extracellular space, the equilibrium pH within cells is lower than the external fluid. It is usual to express acidity in logarithmic form as the pH, defined as the log 1/. Hydrogen is in equilibrium with water which exists in a concentration of 55.5 M with carbon dioxide, a gas exhaled by the lungs (an open buffering system), with proteins, weak acids like hydrogen phosphate, and is involved in many oxidation reduction reactions, and adenosine triphosphate (ATP) synthesis. Since the is in nanomolar concentrations, compared to bicarbonate in millimolar amounts, it is clear that the is involved in many reactions. The hydrogen ion concentration of body fluids is maintained within a narrow range for purposes of regulating normal metabolic and enzymatic processes and critical functions such as fertilization, growth, cell volume regulation, and protein synthesis. There is no reason to dismiss any of the present constructs, and there is benefit in a combined approach. All models have complexity and shortcuts that can help in practice. Electroneutrality and the close interconnection between electrolyte and acid-base balance are important concepts to apply in acid-base diagnoses. Key Messages: Many constructs are helpful to understand acid-base, but these models are not mutually exclusive. Urine chemistry is essential to understanding electrolyte excretion and renal compensations. Acid-base and electrolyte balance are connected not only at the cellular level but also in daily clinical practice. All metabolic acid-base disorders can be approached in the context of the relative losses or gains of electrolytes or a change in the anion gap in body fluids. Summary: This review aims to give new and comprehensive perspective on understanding acid-base balance and identifying associated disorders. However, some of the limitations on compensations are necessary to survival, in that preservation of oxygenation, energy balance, cognition, electrolyte, and fluid balance are connected mechanistically. Compensations for acid-base disturbances within the brain are more complete, while limitations of compensations are more apparent for most systemic disorders. Background: Disorders of acid-base involve the complex interplay of many organ systems including brain, lungs, kidney, and liver.

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