Renal Physiology Acid-Base Homeostasis

Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filteredHCO3 and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3 is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. Clin J Am Soc Nephrol 10: 2232–2242, 2015. doi: 10.2215/CJN.07400715 Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. Normally, systemic acid-base balance is well regulated with arterial pH between 7.36 and 7.44; intracellular pH is usually approximately 7.2. For instance, chronic metabolic acidosis can be associated with decreased bone density, nephrolithiasis, muscle wasting, and progression of CKD (1–3). On a cellular level, many essential cellular processes, metabolic enzymes, and transmembrane transport processes are highly pH sensitive. Although this reviewwill address systemic pH regulation and the role of the kidneys, individual cells also have a variety of mechanisms to regulate their intracellular pH (4). Overall concepts will be emphasized rather than specific pathways or processes, which are well covered elsewhere; references are selective. Basic Concepts Intracellular and extracellular buffers are the most immediate mechanism of defense against changes in systemic pH. Bone and proteins constitute a substantial proportion of these buffers. However, the most important buffer system is the HCO3 /CO2 buffer system. The Henderson–Hasselbach equation (Equation 1) describes the relationship of pH, bicarbonate (HCO3 ), and PCO2: