Acid-Base Homeostasis

Abstract

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 filtered HCO3(-) 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.

Keywords: acid-base equilibrium; acid-base homeostasis; acidosis; bone density; chronic; homeostasis; kidney; nephrolithiasis; pH regulation; renal insufficiency; renal physiology.

Figure 1.

Relative HCO₃⁻ transport along the nephron. Most of the filtered HCO₃⁻ is reabsorbed in the proximal tubule. Virtually no HCO₃⁻ remains in the final urine. CCD, cortical collecting duct; DT, distal convoluted tubule; IMCD, inner medullary collecting duct; TAL, thick ascending limb.

Figure 2.

Relative urinary titratable acid and ammonia in adults on a control or acid loading diet (with NH₄Cl). Reference .

Figure 3.

Schematic representation of HCO₃⁻ reabsorption in the proximal tubule. Most H⁺ secretion occurs through Na⁺/H⁺ exchange, although a component of an H⁺ pump is also present. Carbonic anhydrase (CA), both intracellular and luminal, is important for HCO₃⁻ reabsorption. HCO₃⁻ exits the cell by NBCe1-A.

Figure 4.

Schematic of H⁺ and HCO₃⁻ transport in the types A and B intercalated cells (ICs) in the collecting tubule (details are in the text). AE, anion exchanger.

Figure 5.

Schematic of ammonia (NH₃) production in the proximal tubule. A proximal tubule cell is enlarged to show that glutamine (Gln) is metabolized to ammonium (NH₄⁺) by phosphate-dependent glutaminase (PDG); through a series of steps, the carbon skeleton of glutamine can be metabolized to HCO₃⁻. NH₃ can enter the proximal tubule lumen by either NH₃ diffusion or NH₄⁺ movement on the Na⁺-H⁺ exchanger. AA⁰, neutral amino acids; B*AT1, B-type neutral amino acids transporter; GDH, glutamate dehydrogenase; αKG, alfa keto-glutarate; LAT2, L-type amino acids transporter-2; OAA, oxalo-acetate; PEP, phospho enol-pyruvate; PEPCK, phospho enol-pyruvate carboxy kinase; TCA, XXX.

Figure 6.

Ammonium (NH₄⁺) transport along the nephron. In the thick ascending limb, NH₄⁺ is reabsorbed by the Na⁻K⁻2Cl transporter. In the collecting duct, Rh proteins mediate ammonia (NH₃)/NH₄⁺ transport. The numbers depict the percentages of urinary total NH₃ at each site. Total NH₃ is concentrated in the medulla (details are in the text). Gln, glutamine; PDG, phosphate-dependent glutaminase.