Outside the cells, the pH regulates the rate of absorption of compounds. Inside cells, and in body fluids, pH or hydrogen ion concentration is very tightly controlled. This precision is necessary because almost all the enzymes in the body are influenced by the amount of hydrogen ions present in the solution around them.

The stomach has a pH of 1 (a low pH, a high concentration of hydrogen ions). With this many hydrogen ions, an acid with a pK value of 3 is not going to be able to give away its hydrogen ions (donate hydrogen ions) because there are too many in solution. Rather like a housing market flooded with properties makes it difficult for a vendor to sell their properties. However, a base with a pK of 9 will be only too happy to soak up the spare hydrogen ions. This is the same as a buyer having a great deal of choice when a house market is flooded with properties (a buyer’s market).

Therefore, in the acidic environment of the stomach, the salicylic acid stays in its configuration but quinine becomes positively charge due to the extra hydrogen ions (Figure 8.3). The salicylic acid is therefore uncharged (un-ionized, non-polar) and the quinine is charged (ionized, polar).

Figure 8.3 The balance of acids and bases at a low pH.

The lining of the stomach consists of cell with a lipid membrane, which is non-polar. Any non-polar compound, such as the salicylic acid in this case, is easily absorbed across the membrane. The polar quinine, however, is not absorbed by the non-polar cell membranes.

There is a marked pH change further down the GI tract, with the pH becoming 7.8 in the small intestine. Now the previous situation becomes reversed, as a pH of 7.8 means that there is a much lower concentration of hydrogen ions in solution.

With so few hydrogen ions, an acid with a pK value of 3 will be able to give away (donate) almost as many hydrogen ions as it likes. A similar situation occurs in a housing market when there is a glut of people wanting to buy properties. It makes it so much easier for vendors to sell their property (vendor’s market).

With a compound with a pK of 9 and a base, not many quinine molecules will be able to attach many hydrogen ions to it, because there are so few hydrogen ions. This is the same as having too many buyers for a very small number of properties.

By losing a hydrogen ion the salicylic acid therefore becomes charged (ionized, polar; Figure 8.4) and the quinine, by being unable to attach to a hydrogen ion is uncharged (un-ionized, non-polar).

Figure 8.4 The balance of acids and bases at a high pH.

Like the stomach, the lining of the small intestine is made up of cells with a lipid membrane, which is non-polar. Any non-polar compound, such as the quinine in this case is easily absorbed across the membrane. The polar salicylic acid, however, is not absorbed by the non-polar cell membranes.

The environmental pH therefore has an effect on acids and bases, as different pHs can make them charged (ionized or polar) or uncharged (un-ionized or non-polar). This in turn affects the absorption of an acidic or basic compound through a membrane that is largely non-polar due to its composition of non-polar lipids.

The kidneys are a very active area when it comes to pH (see Figure 18.3, p. 135). The excretion of certain drugs can be altered depending on the pH of the urine.

Under the right conditions, substances such as organic acids that have carboxyl groups (see Figure 5.1, p. 30) can ionize and form negatively charged COO⁻ ions and positively charged H⁺ ions (or protons). This capacity of a molecule to lose or gain a proton is very important in maintaining stability of pH in the bloodstream and how easily a chemical is absorbed or removed from the body (see Chapter 18 ‘Drug excretion’, p. 135). pH is kept very tightly controlled in the plasma.

When there are excess hydrogen ions (low pH; Figure 8.6, top arrow, right to left) the equilibrium is shifted to the left. To restore the correct hydrogen ion concentration (pH), the excess of hydrogen ions will react with the bicarbonate ions (HCO₃⁻) eventually producing carbon dioxide and water.

Figure 8.6 The shift in equilibrium in the bicarbonate buffering system in the blood.

When there is a decrease in hydrogen ions (high pH; Figure 8.6, bottom arrow, left to right), carbon dioxide will combine with water, eventually producing more hydrogen ions and bicarbonate ions. The respiratory centre will then increase respiration to remove excess carbon dioxide from the blood.

There is a large flow of blood through the kidneys and – potentially – a large capability to remove fluids and solutes from the body (see Chapter 18 ‘Drug excretion’, p. 135 and Chapter 26 ‘Cardiovascular disorders’, p. 192). The kidneys are therefore a convenient way to control pH.

Large amounts of bicarbonate ions are continuously filtered into the kidney tubules. The amount of bicarbonate lost therefore acts to control the pH of the blood.