Body Fluid Compartments, Cell Membrane Ion Transport, Electrolyte Concentrations, and Acid-Base Balance

Measurements made in the blood, part of the extracellular compartment, are used in the clinical assessment of acid-base disorders; however, intracellular events determine much of the metabolic importance of these disorders. Intracellular and interstitial compartment acid-base balance is complex and varies in different tissues. This review considers the determination of extracellular pH in the context of ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. A further consideration is the role of these membrane transporters in the generation of acid-base disorders and the associated disruption of electrolyte balance. This review suggests a process of internal and external balance for pH regulation similar to that of potassium, and considers the role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders. Electroneutrality of electrolytes in the extracellular fluid is a fundamental feature of reciprocal changes in Cl^- or non-Cl^- anions and HCO₃^-. Normal mechanisms for protecting cell pH and producing normal gastrointestinal and renal secretions in healthy states also may result in disease when abnormal. In a similar manner, organic anions such as ketoacid anions and lactate, normally transported as fuels between organs, result in acid-base disturbances in disease. Understanding the genomic basis of these transporters may contribute to specific treatments.