Renal Acid Excretion

Overview
  • Renal elimination of hydrogen ions occurs through tubular secretion; however, hydrogen ions can be secreted in two chemical forms, either as simple hydrogen ions (H+) or as part of an ammonium molecule (NH4+). Whatever the form, secretion of hydrogen is always accompanied by generation of a novel bicarbonate molecule which is subsequently added to the ECF. Consequently, elimination of hydrogen by the kidneys is always accompanied by replenishment of the Weak Base form of the bicarbonate buffer in the extracellular fluid. It should be pointed out that urinary secretion of H+ also occurs during tubular bicarbonate resorption as discussed in renal bicarbonate excretion. However, hydrogen secreted in this process is immediately resorbed and thus does not contribute to net hydrogen secretion by the kidney.
Free H+ Secretion
  • Overview
    • Secretion of hydrogen in its free, ionized form (H+) occurs in the late distal tubule and collecting ducts. As mentioned, secretion of H+ occurs in conjunction with novel generation of bicarbonate which is subsequently added to the extracellular fluid. Interestingly, tubular secretion of free H+ can be stimulated by the presence of aldosterone.
  • Mechanism:
    • Direct secretion of free, ionized hydrogen occurs in Intercalated Cells and begins with the action of cytosolic carbonic anhydrase which uses a molecule of dissolved CO2 to generate H+ and HCO3-. A Luminal H+ ATPase then secretes the newly generated H+ into the tubular lumen via primary active transport. The newly generated HCO3- molecule is transported past the basolateral membrane and into the extracellular fluid through a bicarbonate porter.
Ammonium Secretion
  • Overview
    • Secretion of hydrogen as part of an ammonium molecule occurs in the proximal tubule. Once again, net secretion of hydrogen into the tubular lumen is accompanied by novel generation of bicarbonate which is subsequently added to the extracellular fluid.
  • Mechanism:
    • Secretion of hydrogen as part of ammonium begins with the transport of extracellular fluid glutamine into the tubular epithelial cell. Glutamine is then enzymatically converted into two ammonia molecules (NH3) and two bicarbonate ions (HCO3-). The ammonia molecules are then loaded with a free H+ ion, thus making Ammonium (NH4+) which is subsequently secreted into the tubule by a Na+-NH4+ Antiporter. In contrast, the newly-generated HCO3- molecules are transported past the basolateral membrane and into the extracellular fluid through a bicarbonate porter.
Urine Buffering
  • Overview
    • Although hydrogen can be secreted in its simple ionic form, the tubular epithelial barrier cannot retain extremely high concentrations of free H+ in the tubular fluid without backleak into the extracellular fluid. In fact the minimum achievable urine pH is roughly 4.5 with any additional hydrogen ions eventually backleaking through the tubular epithelium and into the ECF. In the absence of compensatory mechanisms, very little free hydrogen ions could be directly secreted into the urine as the urine pH would rapidly drop to 4.5. However, a variety of urinary buffers help absorb secreted free hydrogen ions and thus allow for large amounts of free H+ secretion without unsustainable drops in urinary pH. The two most physiologically important urinary buffers are the phosphate buffer and the ammonia buffer.
  • Phosphate Buffer
    • Inorganic Phosphate (HPO42-) is freely filtered through the glomerulus and much of it is not resorbed (See: Regulation of Phosphate Excretion). As discussed in phosphate buffer, inorganic phosphate is an excellent buffer as it can reversibly absorb free H+, thus generating H2PO4-. In this way, large amounts of free H+ can be secreted and yet not significantly reduce urinary pH due to the capacity of inorganic phosphate to absorb the secreted hydrogen ions.
  • Ammonia Buffer
    • Ammonia (NH3) is a product of physiological amino acid metabolism and is present in large quantities throughout the extracellular fluid. The late distal tubule and collecting ducts are highly permeable to ammonia which is a Weak Base and readily absorbs free hydrogen ions that have been secreted into the tubule, thus generating ammonium (NH4+). However, the late distal tubule and collecting ducts are highly impermeable to the positively charged ammonium, which essentially becomes trapped within the tubule and is thus ultimately secreted within the urine. It is important to note that the urinary ammonium generated by buffering in the late distal tubule and collecting duct is derived from a mechanistically different source from the ammonium directly secreted at the proximal tubule, although there is chemically no difference between these ammonium molecules.