Acids

Acids are substances that release hydrogen ions when dissolved in water (H₂O). An acid in solution increases the amount of free hydrogen ions in that solution. The strength of an acid is measured by how easily it releases a hydrogen ion in solution. A strong acid, such as hydrochloric acid (HCl), separates (dissociates) completely in water and readily releases all of its hydrogen ions (Fig. 14-1).

FIG. 14-1 Release of hydrogen ions by a strong acid (hydrochloric acid) in which the strong acid completely dissociates in water.

A weak acid does not completely separate in water; it releases only some of its hydrogen ions. In the following example, each molecule of acetic acid (CH₃COOH), a weak acid, contains a total of four hydrogen molecules. When acetic acid combines with water (Fig. 14-2), it releases only one of its four hydrogen molecules. The other three hydrogen molecules remain bound to the acetic acid molecule (CH₃COO⁻).

FIG. 14-2 Release of hydrogen ions by a weak acid (acetic acid) in which the weak acid only partially dissociates in water and most of its hydrogen ions remain bound.

Bases

A base is a substance that binds free hydrogen ions in solution. Thus bases are “hydrogen acceptors” that lower the amount of free hydrogen ions in solution. Strong bases bind hydrogen ions easily. Examples of strong bases include sodium hydroxide (NaOH) and ammonia (NH₃).

Weak bases bind hydrogen ions less readily. Examples of weak bases are aluminum hydroxide (AlOH₃) and bicarbonate (). Although bicarbonate is a weak base, the many bicarbonate ions in the body are very important in preventing major changes in body fluid pH.

Buffers

Buffers are critical in keeping body fluid pH at normal levels because they can react in two ways: either as an acid (releasing a hydrogen ion) or as a base (binding a hydrogen ion). How a buffer reacts when dissolved in water depends on the existing acid-base balance of that fluid. Buffers always try to bring the fluid as close as possible to the normal body fluid pH of 7.35 to 7.45. If the fluid is basic (with few free hydrogen ions), the buffer releases hydrogen ions into the fluid (Fig. 14-3). If the fluid is acidic (with many free hydrogen ions), the buffer acts as a base, binding some of the excess hydrogen ions. In this way, buffers act like hydrogen ion “sponges,” soaking up hydrogen ions when too many are present and squeezing out hydrogen ions when too few are present. This flexibility allows buffers to keep body fluid pH in the normal range.

FIG. 14-3 Action of buffer in solution.

Liquids with a pH of 7.0 are neutral; they have a free hydrogen ion level in which the amount and strength of acids and bases are equal. Fig. 14-4 shows the concept of neutral pH. This figure shows that the combined strength and amount of all acids are equal to the combined strength and amount of all bases in a given solution. This is close to the actual case in human physiology. With human acid-base homeostasis, the relative amounts and strengths of acids and bases are nearly equal and, normally, hydrogen ion production is balanced with hydrogen ion loss so that the overall free hydrogen ion levels remain constant.

FIG. 14-4 Concept of acidic versus normal pH. (A = acid; B = base.)

Liquids with a pH ranging from 1.0 to 6.99 have more or stronger (or both) acids compared with the amount or strength (or both) of bases. These liquids are acidic (see Fig. 14-4), which means that more free hydrogen ions are being released than bound, increasing the amount of free hydrogen ions in the liquid.

Liquids with a pH ranging from 7.01 to 14.0 have more or stronger (or both) bases compared with the amount or strength (or both) of acids. These liquids are basic, which means that more hydrogen ions are being bound than released, decreasing the amount of free hydrogen ions (Fig. 14-5).

FIG. 14-5 Concept of alkaline versus normal pH. (A = acid; B = base.)

Bicarbonate Ions

Body fluids contain many different types of acids and a few types of bases. The most common base in human body fluid is bicarbonate (); the most common acid is carbonic acid (H₂CO₃). In health, the body keeps these substances at a constant ratio of 1 molecule of carbonic acid to 20 free bicarbonate ions (1 : 20) (Fig. 14-6). To maintain this ratio, both carbonic acid and bicarbonate must be carefully controlled. This constant ratio is related to balancing the production and elimination of carbon dioxide (CO₂) and hydrogen ions (H⁺).

FIG. 14-6 Normal ratio of carbonic acid to bicarbonate is 1 : 20.

Relationship Between Carbon Dioxide and Hydrogen Ions

A key concept in understanding acid-base balance is the carbonic anhydrase equation. This equation, driven by the enzyme carbonic anhydrase, shows how hydrogen ion levels and carbon dioxide levels are directly related to one another, so that an increase in one causes an equal increase in the other (Fig. 14-7).

FIG. 14-7 The carbonic anhydrase equation showing that the concentration of carbon dioxide is directly related to the concentration of hydrogen ions.

Carbon dioxide is a gas that forms carbonic acid when combined with water, making carbon dioxide a part of carbonic acid. Carbonic acid is not stable, and the body needs to keep a 1 : 20 ratio of carbonic acid to bicarbonate. When carbonic acid is formed from water and carbon dioxide, it begins to separate into free hydrogen ions and bicarbonate ions. Therefore the carbon dioxide content of a fluid is directly related to the amount of hydrogen ions in that fluid. Whenever conditions cause carbon dioxide to increase, more free hydrogen ions are created. Likewise, whenever free hydrogen ion production increases, more carbon dioxide is produced.

When excess carbon dioxide is produced, the amount of carbon dioxide increases and the equation shifts to the right, causing an increase in hydrogen ions (and a decrease in pH), as shown in Fig. 14-8. When very little carbon dioxide is produced, no free hydrogen ions are created by this equation. When excess hydrogen ions are produced or brought into the body, the carbonic anhydrase equation shifts to the left, causing the creation of more carbon dioxide, as shown in Fig. 14-9. When the amount of free hydrogen ions in body fluids is low, no extra carbon dioxide is produced.

FIG. 14-8 Increased carbon dioxide levels force the equation to the right and increase the concentration of hydrogen ions proportionately.

FIG. 14-9 Increased hydrogen ion levels force the equation to the left and increase the concentration of carbon dioxide levels proportionately.

How is the relationship between free hydrogen ions and carbon dioxide helpful? Carbon dioxide is a gas that can be eliminated during exhalation, and this action is important for acid-base balance. When any condition causes the hydrogen ion concentration of body fluids to increase, extra CO₂ is produced in the same proportion. This extra CO₂ is eliminated during exhalation, helping to bring the hydrogen ion concentration down to normal. Whenever the CO₂ level changes, the pH changes to the same degree, in the opposite direction. Thus when the CO₂ level of a liquid increases, the pH drops, indicating more free hydrogen ions (more acidic). On the other hand, when the CO₂ level of a liquid decreases, the pH rises, indicating fewer free hydrogen ions (more alkaline).

An increase in bicarbonate causes the amount of hydrogen ions to decrease and the pH to increase, or become more alkaline (basic). On the other hand, an increase in the CO₂ level causes the free hydrogen ion level to increase and the pH to decrease, or become more acidic.

Because the kidneys control bicarbonate levels and the lungs control CO₂ levels in the healthy person, pH is also described as the function of the kidneys divided by the function of the lungs (Fig. 14-10).

FIG. 14-10 Contribution of pH balance by kidney and lung function.

Sources of Acids and Bicarbonate

Whenever acids are present in body fluids, free hydrogen ions are dissociated and must be controlled for pH balance. How are acids and hydrogen ions produced? Remember that whole body human function is dynamic and continuously working. The processes that allow the body to perform its work continuously generate acids and hydrogen ions as waste products of metabolism.

Normal metabolism of carbohydrate, protein, and fat creates natural waste products. Carbohydrate metabolism forms carbon dioxide (CO₂). Carbon dioxide is exhaled by the lungs during breathing. One factor that determines blood pH is how much CO₂ is produced by body cells during metabolism versus how rapidly that CO₂ is removed by breathing. Protein breakdown forms sulfuric acid. Fat breakdown forms fatty acids and ketoacids.

Incomplete breakdown of glucose, which occurs whenever cells metabolize under anaerobic (no oxygen) conditions, forms lactic acid. Anaerobic conditions occur with hypoxia, sepsis, and shock. Incomplete breakdown of fatty acids, occurring when large amounts of fatty acids are being metabolized, forms ketoacids.

Destruction of cells allows cell contents to be released. Some cell structures (e.g., lysosomes) contain acids. When these acids are released into the extracellular fluid (ECF), free hydrogen ions are dissociated.

Bicarbonate, a weak base, is the main buffer of the ECF. It comes from the intestinal absorption of ingested bicarbonate, pancreatic production of bicarbonate, movement of cellular bicarbonate into the ECF, kidney reabsorption of filtered bicarbonate, and the breakdown of carbonic acid. Once bicarbonate is in the ECF, it is kept at a level 20 times greater than that of carbonic acid.

Chemical Acid-Base Control Actions and Mechanisms

Buffers are the first line of defense against changes in the amount of free hydrogen ions. Because they are always present in body fluids, buffers act fast to reduce or raise the amount of free hydrogen ions to normal. By acting as hydrogen ion “sponges,” buffers can bind hydrogen ions when too many are present or release hydrogen ions when not enough are present. Buffers are composed of chemicals or proteins.

Chemical buffers are paired mixtures—usually a weak base and an acid salt. The two most common chemical buffers are bicarbonate (which is active in both the extracellular fluid [ECF] and intracellular fluid [ICF]) and phosphate (which is active in the ICF).

Protein buffers are the most common buffers. Proteins in body fluids can either bind or release free hydrogen ions as needed. Both ICF and ECF proteins serve as buffers. Extracellular protein buffers are albumin and globulins. A major cell protein buffer is hemoglobin. Hemoglobin buffers hydrogen ions directly and also buffers acids formed during the production of carbon dioxide. When the amount of free hydrogen ions in the blood increases, some of the excess hydrogen ions cross the membranes of red blood cells and bind to the large numbers of hemoglobin molecules in each red blood cell. This binding of hydrogen ions to hemoglobin results in fewer hydrogen ions remaining in the blood, bringing blood pH back up toward normal.

Respiratory Acid-Base Control Actions and Mechanisms

When chemical buffers alone cannot prevent changes in blood pH, the respiratory system is the second line of defense against changes. Breathing controls the amount of free hydrogen ions by controlling the amount of carbon dioxide (CO₂) in arterial blood. Remember, because CO₂ is converted into hydrogen ions through the carbonic anhydrase reaction, the CO₂ level is directly related to the hydrogen ion level. Breathing rids the body of the excess CO₂ created through metabolism.

The amount of CO₂ in venous blood increases during normal metabolism. This CO₂ is moved in the blood to the lung capillaries. Because the amount (pressure) of CO₂ is far higher in capillary blood than in the air in the alveoli, CO₂ diffuses freely from the blood into the alveolar air. Once in the alveoli, CO₂ is exhaled during breathing and is lost from the body. Because the amount (pressure) of CO₂ in atmospheric air is nearly zero, CO₂ usually continues to be exhaled even when breathing is impaired.

Respiratory regulation of acid-base balance is under the control of the central nervous system (Fig. 14-11). Special receptors in the respiratory areas of the brain are sensitive to changes in the amount of CO₂ in brain tissues. As the amount of CO₂ begins to rise above normal in brain blood and tissues, these central receptors trigger the neurons to increase the rate and depth of breathing (hyperventilation). As a result, more CO₂ is exhaled (“blown off”) from the lungs and the amount of CO₂ in the ECF decreases. When the amount of arterial CO₂ returns back down to normal, the rate and depth of breathing return to levels that are normal for the person.

FIG. 14-11 Neural regulation of respiration and hydrogen ion concentration. (PaCO₂, Partial pressure of arterial carbon dioxide; H⁺, hydrogen ion.)

If the amount of ECF free hydrogen ions is too low, then the amount of CO₂ also is too low. Central receptors sense these low CO₂ levels and stop or slow the neuron activity in the respiratory centers of the brain, decreasing the rate and depth of breathing (hypoventilation). As a result, less CO₂ is lost through the lungs and more CO₂ is retained in arterial blood. This retention of already-formed CO₂, together with the normal production of CO₂ from metabolism, results in a rapid return of the arterial CO₂ levels (and hydrogen ion levels) back up to normal. When these levels are normal, the rate and depth of breathing also return to normal levels.

The respiratory system’s response in acid-base balance is rapid. Changes in the rate and depth of breathing occur within minutes after changes in the hydrogen ion level or CO₂ level of the ECF occur.

Kidney Acid-Base Control Actions and Mechanisms

The kidneys are the third line of defense against wide changes in body fluid pH. Kidney actions are stronger for regulating acid-base balance but take longer than chemical and respiratory actions to completely respond. (They take 24 to 48 hours to respond.) When blood pH changes are persistent, kidney actions that increase excretion and reabsorption rates of acids or bases (depending on the direction of the pH changes) begin to operate. These actions are kidney movement of bicarbonate, formation of acids, and formation of ammonium.

Kidney movement of bicarbonate is the first kidney pH control action. It occurs in the kidney tubules in two ways: (1) kidney movement of bicarbonate produced elsewhere in the body and (2) kidney movement of bicarbonate produced in the kidneys. Much of the bicarbonate made in other body areas is excreted in the urine. When blood hydrogen ion levels are high, this bicarbonate is reabsorbed from the kidneys back into circulation, where it can help buffer excess hydrogen ions. In this situation, the kidney tubules also can make additional bicarbonate and reabsorb it for an increased buffer effect. When blood hydrogen ion levels are low, the bicarbonate remains in the urine and is excreted.

Formation of acids is the second kidney pH control action. It occurs through the phosphate-buffering system inside the cells of the kidney tubules. When the newly created bicarbonate made in the kidney cells is reabsorbed into the blood along with sodium, the urine has an excess of anions, including phosphate (). This negatively charged fluid draws hydrogen ions (which carry a positive charge) into the urine. Once the hydrogen ion is in the urine, it binds to phosphate ions, forming an acid, H₂PO₄, which is then excreted in the urine.

Formation of ammonium is the third kidney pH control action. Ammonia (NH₃), which is formed during normal protein breakdown, is converted into ammonium (). The ammonia is first secreted into the urine, where it can combine with excess hydrogen ions to form ammonium. The ammonium “traps” the hydrogen ions and then allows them to be excreted in the urine. The result is a loss of hydrogen ions and an increase in blood pH.