Many chemical reactions are affected by the acidity of the solution in which they occur. In order for a particular reaction to occur or to occur at an appropriate rate, the pH of the reaction medium must be controlled. Such control is provided by buffer solutions, which are solutions that maintain a particular pH. Biochemical reactions are especially sensitive to pH. Most biological molecules contain groups of atoms that may be charged or neutral depending on pH, and whether these groups are charged or neutral has a significant effect on the biological activity of the molecule.

     In all multicellular organisms, the fluid within the cell and the fluids surrounding the cells have a characteristic and nearly constant pH. This pH is maintained in a number of ways, and one of the most important is through buffer systems. Two important biological buffer systems are the dihydrogen phosphate system and the carbonic acid system.

     The phosphate buffer system operates in the internal fluid of all cells. This buffer system consists of dihydrogen phosphate ions (H2PO4-) as hydrogen-ion donor (acid) and hydrogen phosphate ions (HPO42-) as hydrogen-ion acceptor (base). These two ions are in equilibrium with each other as indicated by the chemical equation below.

H2PO4-(aq) H+(aq) + HPO42-(aq)

If additional hydrogen ions enter the cellular fluid, they are consumed in the reaction with HPO42-, and the equilibrium shifts to the left. If additional hydroxide ions enter the cellular fluid, they react with H2PO4-, producing HPO42-, and shifting the equilibrium to the right. The equilibrium-constant expression for this equilibrium is

Ka =
[H +] [HPO42-]


The value of Ka for this equilibrium is 6.23 10-8 at 25°C. From this equation, the relationship between the hydrogen-ion concentration and the concentrations of the acid and base can be derived.

[H +]
= Ka

Thus, when the concentrations of H2PO4- and HPO42- are the same, the value of the molar concentration of hydrogen ions is equal to the value of the equilibrium constant, and the pH is equal to the pKa (-log Ka), namely 7.21. Buffer solutions are most effective at maintaining a pH near the value of the pKa. In mammals, cellular fluid has a pH in the range 6.9 to 7.4, and the phosphate buffer is effective in maintaining this pH range.

     Another biological fluid in which a buffer plays an important role in maintaining pH is blood plasma. In blood plasma, the carbonic acid and hydrogen carbonate ion equilibrium buffers the pH. In this buffer, carbonic acid (H2CO3) is the hydrogen-ion donor (acid) and hydrogen carbonate ion (HCO3-) is the hydrogen-ion acceptor (base).

H2CO3(aq) H+(aq) + HCO3-(aq)

This buffer functions in exactly the same way as the phosphate buffer. Additional H+ is consumed by HCO3- and additional OH- is consumed by H2CO3. The value of Ka for this equilibrium is 7.9 10-7, and the pKa is 6.1 at body temperature. In blood plasma, the concentration of hydrogen carbonate ion is about twenty times the concentration of carbonic acid. The pH of arterial blood plasma is 7.40. If the pH falls below this normal value, a condition called acidosis is produced. If the pH rises above the normal value, the condition is called alkalosis.

     The concentrations of hydrogen carbonate ions and of carbonic acid are controlled by two independent physiological systems. Carbonic acid concentration is controlled by respiration, that is through the lungs. Carbonic acid is in equilibrium with dissolved carbon dioxide gas.

H2CO3(aq) CO2(aq) + H2O(l)

An enzyme called carbonic anhydrase catalyzes the conversion of carbonic acid to dissolved carbon dioxide. In the lungs, excess dissolved carbon dioxide is exhaled as carbon dioxide gas.

CO2(aq) CO2(g)

The concentration of hydrogen carbonate ions is controlled through the kidneys. Excess hydrogen carbonate ions are excreted in the urine.

     The much higher concentration of hydrogen carbonate ion over that of carbonic acid in blood plasma allows the buffer to respond effectively to the most common materials that are released into the blood. Normal metabolism releases mainly acidic materials: carboxylic acids such as lactic acid (HLac). These acids react with hydrogen carbonate ion and form carbonic acid.

HLac(aq) + HCO3-(aq) Lac-(aq) + H2CO3(aq)

The carbonic acid is converted through the action of the enzyme carbonic anhydrase into aqueous carbon dioxide.

H2CO3(aq) CO2(aq) + H2O(l)

An increase in CO2(aq) concentration stimulates increased breathing, and the excess carbon dioxide is released into the air in the lungs.

     The condition called respiratory acidosis occurs when blood pH falls as a result of decreased respiration. When respiration is restricted, the concentration of dissolved carbon dioxide in the blood increases, making the blood too acidic. Such a condition can be produced by asthma, pneumonia, emphysema, or inhaling smoke.

     Metabolic acidosis is the decrease in blood pH that results when excessive amounts of acidic substances are released into the blood. This can happen through prolonged physical exertion, by diabetes, or restricted food intake. The normal body response to this condition is increases breathing to reduce the amount of dissolved carbon dioxide in the blood. This is why we breathe more heavily after climbing several flights of stairs.

     Respiratory alkalosis results from excessive breathing that produces an increase in blood pH. Hyperventilation causes too much dissolved carbon dioxide to be removed from the blood, which decreases the carbonic acid concentration, which raises the blood pH. Often, the body of a hyperventilating person will react by fainting, which slows the breathing.

     Metabolic alkalosis is an increase in blood pH resulting from the release of alkaline materials into the blood. This can result from the ingestion of alkaline materials, and through overuse of diuretics. Again, the body usually responds to this condition by slowing breathing, possibly through fainting.

     The carbonic acid-hydrogen carbonate ion buffer works throughout the body to maintain the pH of blood plasma close to 7.40. The body maintains the buffer by eliminating either the acid (carbonic acid) or the base (hydrogen carbonate ions). Changes in carbonic acid concentration can be effected within seconds through increased or decreased respiration. Changes in hydrogen carbonate ion concentration, however, require hours through the relatively slow elimination through the kidneys