Buffers, Lungs, and Kidneys Together Maintain Acid-Base Balance

Normal blood pH is approximately 7.4; normal cellular func­tion requires a pH close to this value. Three systems maintain acid-base homeostasis: (1) intracellular and extracellular buffers, (2) the lungs, and (3) the kidneys.

Usually maintaining acid-base balance requires preventing excess acid in the body. Acid is constantly produced in the body as a byproduct of metabolism. The amount of acid produced varies depending on changes in diet, exercise, other organ func­tions, and in birds the phases of the egg-laying cycle. Therefore the systems that maintain acid-base homeostasis must adapt to changes in the acid load. Less often, there is an excess base load, which also must be eliminated.

Several intracellular and extracellular buffers titrate H⁴ to maintain a physiological pH. These include hemoglobin and other proteins, carbonate in bone, phosphate, and bicarbonate (HCO₃ ). These buffers rapidly normalize the pH after acute alterations in the acid load, unless the buffering capacity is exceeded. In addition, during chronic metabolic acidosis, bone provides a reservoir of buffer that contributes to maintenance of systemic pH. In this condition, excess H⁺ and low HCO₃" in the extracellular fluid promote physicochemical as well as osteoclast-mediated dissolution of bone, releasing carbonate, which buffers H^,.

The respiratory system also responds rapidly to maintain normal blood pH by altering the rate of removal of carbon dioxide (CO₂) from the blood. The enzyme carbonic anhydrase (CA), present in red blood cells and many other cells, catalyzes the following reaction:

CA

CO₂ + H₂O precisely.

Most of the secreted H⁴ is transported across the apical plasma membrane by the following three transporters: (1) a sodium ion (Na⁺)∕H^f exchanger, (2) an electrogenic H⁺- adenosinetriphosphatase (ATPase) pump, and an H',potas­sium ion (K⁺)-ATPase pump. I he Na⁺∕H* exchanger exchanges luminal Na⁺ for intracellular H^,. The Na^t gradient generated by basolateral Na*,K⁴-ATPase drives Na⁺∕H^, exchange (sec­ondary active transport). Na7H⁺ exchange is the main route of H⁺ secretion in the proximal tubule. The electrogenic H^f- ATPase pump actively transports intracellular H^f across the apical plasma membrane and contributes a net positive charge to the tubule fluid. The H*,K' -ATPase pump, which is similar to the gastric proton pump, actively secretes acid by elec­trically neutral exchange of intracellular H’ for K⁺ in the tubule fluid. Although the H -ATPase pump is responsible for most H⁺ secretion by the collecting duct, the H’,K⁺-ATPase pump may contribute equally or exceed the acid secretion rate of the H⁺-ATPase pump under some conditions.

Buffering of the tubule fluid is necessary for efficient acid excretion. Buffers accept secreted H^t and minimize the decrease in tubule fluid pH that would otherwise follow rapid H’ secretion by the epithelial cells. In mammals the most important buffers are bicarbonate and phosphate. In birds, urates also contribute to titration of secreted acid. Figure 44-1 illustrates the removal of acid by intraluminal buffers.

In the proximal tubule, HCO₃ is the most important intra­luminal buffer, for two main reasons, first, the concentration of HCO₃" in the tubule fluid is high.

Filtered phosphate also buffers the tubule fluid. Secreted H⁺ titrates HPO₄²" to form H₂PO₄". Because the titrated form is a charged molecule, it is lipid insoluble. Furthermore, there is little transport of monovalent P₁ (H₂PO₄") on the NaPi-2 transporter. Thus the secreted acid is retained in the tubule fluid. Similarly in birds, titration of luminal urate forms uric acid, which traps secreted protons in the tubule fluid. Besides being lipid insoluble, uric acid also has a low aqueous per­meability, and thus a significant portion of acid is removed as uric acid precipitates.