Acid–Base Balance

The normal pH of the blood is maintained in the narrow range of 7.35 – 7.45. The maintenance
of blood pH is an important homeostatic mechanism of the body. The body’s acid-base balance
plays a crucial role in maintaining the blood pH.

Production of acids by the body

The metabolism of the body is accompanied by an overall production of acids. These

include the volatile acids like carbonic acid or volatile acids such as lactic acid, sulfuric acid,
phosphoric acid etc. Carbonic acid is formed from the metabolic product of CO 2, Lactic acid is
produced in anaerobic metabolism, sulfuric acid is generated from proteins (sulfur containing
amino acids). Phosphoric acid is derived from organic phosphates (e.g. phospholipids). All these
acids add up H+ ions to the blood. A diet rich in animal proteins results in more acid production
by the body.

Production of bases by the body

The formation of basic compounds in the body in normal circumstances is negligible.

Some amount of bicarbonate is generated from the organic acids such as lactate and citrate. A
vegetarian diet has a tendency for a net production of bases. This is due to the fact that
vegetarian diet produces salts of organic acids such as sodium lactate which can utilize H+ ions
produced in the body. For this reason, a vegetarian diet has an alkalizing effect on the body.

Maintenance of blood pH

The body has developed three lines of defence to regulate the body’s acid base balance and
maintain the blood pH around 7.4

1. Blood buffers
2. Regulation by lungs or respiratory mechanism
3. Regulation by the kidney or renal mechanism.

I. Blood buffers

A buffer may be defined as a solution of weak acid (HA) and its salt (BA) with a strong
base. The buffer resists the changes in pH by the addition of acid or alkali and the buffering
capacity is dependent on the absolute concentration of salt and acid.

The blood contains 3 buffer systems

1. Bicarbonate buffer
2. Phosphate buffer
3. Protein buffer
 1. Bicarbonate buffer system

Sodium bicarbonate and carbonic acid (NaHCO3 – HCO3) is the most predominant buffer
system of the extracellular fluid, particularly the plasma.

Blood pH and the ratio of HCO3 to H2CO3

The plasma bicarbonate (HCO3) concentration is around 24 mmol/l (22-26 mmol/l).

Carbonic acid is a solution of CO2 in water. At a blood pH of 7.4 the ratio of bicarbonate to
carbonic acid is 20:1. Thus the bicarbonate concentration is 20 times than carbonic acid in
the blood. This is referred to as alkali reserve and is responsible for the effective buffering of
H+ ions. In normal circumstances, the concentration of bicarbonate and carbonic acid
determines the pH of blood.

2. Phosphate buffer system

Sodium dihydrogen phosphate and disodium hydrogen phosphate (NaH 2PO4 – Na2HPO4)
constitute the phosphate buffer. It is mostly an intracellular buffer.

3. Protein buffer system

The plasma proteins and haemoglobin together constitute the protein buffer system of the
blood.

Hemoglobin buffer system

The buffering capacity of hemoglobin is due to the presence of imidazole groups in its histidine
residues. The degree of dissociation of the imidazole groups is dependent upon the degree of
oxygenation of Hb. If hemoglobin is oxygenated, it is more acidic and therefore exists in its
dissociated form. When it is not bound with oxygen, it will be in the reduced form.

In the tissues, where oxygen tension is reduced, HbO2 dissociates to give oxygen to the tissues. In
turn, the CO2 produced in the tissues will combine with H 2O to form H2CO3, which dissociates to
H+ and HCO3 The reduced Hb devoid of O2 combines with H+ ions to form HHb resulting a very
little change in the pH.

When the blood returns to the lungs, O 2 tension in the lungs is high resulting in the oxygenation
of Hb. As mentioned earlier, HbO 2 has lesser affinity to H + and releases it. It combines with
HCO3 ions to form H2CO3 that dissociates to H2O and CO2..
 Figure 1 Buffering action of Haemoglobin

It has been found that more than 80% of the buffering capacity of blood is due to red blood cells.
But the buffered HCO3is transported in the plasma. The process of transport of the formed
HCO3 from the RBCs into the plasma needs chloride ions and the phenomenon is called as
Hamberger’s chloride bicarbonate shift.
 When CO2 liberated from the tissues enters the RBC via plasma, it combines with water
to form carbonic acid, the reaction catalysed by an enzyme called as carbonic anhydrase. The
same enzyme can also dissociate carbonic acid to carbon dioxide and water. Carbonic acid
dissociates into HCO3and H+ ions.
The formed bicarbonate is exchanged for one chloride ion with the plasma. The chloride
that enters the cell forms neutral potassium chloride in the cell. The bicarbonate that enters the
plasma reacts with the sodium ions to form sodium bicarbonate. Thus, the bicarbonate ions are
transported in the plasma.

Figure 2 Hambergers Chloride Bicarbonate Shift

Regulation by Respiratory mechanism

Respiratory mechanism plays an important role in the regulation of acid-base balance because
the respiratory centre is sensitive to the changes in pCO2 .

The partial pressure of carbon dioxide (PCO2) is the measure of carbon dioxide within
arterial or venous blood).
Arterial blood is the oxygenated blood in the circulatory system found in the pulmonary
vein, the left chambers of the heart, and in the arteries. It is bright red in color, while
venous blood is dark red in color (but looks purple through the translucent skin). It is the
contralateral term to venous blood.

Blood that has passed through the capillaries of various tissues other than the lungs, is
found in the veins, in the right chambers of the heart, and in pulmonary arteries, and is
usually dark red as a result of a lower content of oxygen.

If there is an increase in pCO 2, increased respiration occurs, helping to remove the excess
CO2. This continues until the blood regains normal pCO 2 and pH. Similarly a fall in the pCO 2
leads to slow, shallow respiration, hypoventilation and retention of CO2.

Regulation by renal mechanism

The lungs can remove only volatile acids like CO 2 but not the organic acids like lactic acid and
pyruvic acids. These acids are effectively buffered by the bicarbonate system, but at the expense
of the bicarbonate, which is called as the alkali reserve of the body. Lungs can eliminate
H2CO3, but cannot restore bicarbonate. This is done by the kidneys, which are the ultimate
regulators of acid base balance. In acidemia, inorder to bring the low pH to normal, the excessive
H+ ions should be excreted and bicarbonate excretion should be reduced. This is done by
excreting
a highly acidic urine (pH 4.5). On the other hand, during alkalemia, the kidneys excrete the
excess bicarbonate producing an alkaline urine (pH 8.2). The three important mechanisms
attributed by the kidneys to regulate the blood pH are

(i) Reabsorption of bicarbonate

(ii) Buffering by phosphate buffers
(iii) Formation of ammonium ions (NH4+).
Disorders of acid base balance

The acid base balance disorders are mainly classified as follows

1. Acidosis - A decline in blood pH

a. Metabolic acidosis due to a decrease in bicarbonate
b. Respiratory acidosis due to an increase in carbonic acid.

2. Alkalosis – A rise in blood pH

a. Metabolic alkalosis due to an increase in bicarbonate,
b. Respiratory alkalosis due to a decrease in carbonic acid.

In the actual clinical situation mixed type of disorders are common.

BUFFERS
Buffer. A solution resisting pH change on addition of acid (i.e. H +) or alkali (OH-); absorbing
protons from acids and releasing them on, addition ‘of alkali. Usually consists of a mixture of a
weak acid and’ its conjugate base, or vice versa. Intracellular and extracellular buffers may
differ; thus the commonest intracellular buffer is the acid-base pair H,P0,--HP0,2- and such
organic phosphates as ATP, but the bicarbonate buffer system (H 2C03- HCO,-) is common
extracellularly, as in vertebrate blood plasma, where plasma proteins are also a major buffer
system, HAEMOGLOBIN acts as a buffer during the CHLORIDE SHIFT. If pH varies,
PROTEIN shape and function may ’be affected.

OR
A buffer may be defined as a solution which resists the change in pH that will occur on addition
of small quantities of acid or base to the solution. Buffers are mixtures of weak acid and its salt
or weak base and its salt. The pH of the solution is defined as the negative logarithm of hydrogen
ion concentration. The pH of buffers are determined by Henderson Haselbach equation, which is
derived as follows
The pH of blood is 7.4 and it should be maintained constant. If pH increases above 7.5, alkalosis
occurs and beyond 7.8 death occurs.

If it falls below, 7.3, acidosis occurs and below 7.0 is incompatible for life. Due to metabolism
and dietary intake, large quantities of acids and bases are produced in the body and they have to
be transported through bloodfor elimination. This should occur without any major changes in the
pH. This is effectively done in the body by means of the buffers present in the blood and by two
mechanisms, namely the respiratory mechanism and the renal mechanism.
The buffer systems of blood are as follows
The numerators are acid components and the denominators are salts.

Since the concentrations of phosphate and organic acids are low in plasma, they do not play a
major role in regulation of pH. The major buffer in plasma is bicarbonate buffer and the pKa of
carbonic acid is 6.1. Substituting it in the Henderson Hasselbach equation,

To effectively maintain the pH of blood, according to Henderson Hasselbach equation, the ratio
of bicarbonate to carbonic acid should be 20 : 1.
 pH

pH Definition- pH is defined as the negative logarithm of H+ ion concentration. Hence the

meaning of the name pH is justified as the power of hydrogen.

pH, quantitative measure of the acidity or basicity of aqueous or other liquid solutions. The term,
widely used in chemistry, biology, and agronomy, translates the values of the concentration of
the hydrogen ion—which ordinarily ranges between about 1 and 10−14 gram-equivalents per litre
—into numbers between 0 and 14. In pure water, which is neutral (neither acidic nor alkaline),
the concentration of the hydrogen ion is 10−7 gram-equivalents per litre, which corresponds to a
pH of 7. A solution with a pH less than 7 is considered acidic; a solution with a pH greater than 7
is considered basic, or alkaline.

Exactly 100 years ago, Carlsberg ‘s director of chemistry, Søren Sørensen, developed a vital
diagnostic tool for measuring acidity, thus helping to detect digestive , respiratory and metabolic
disorders. The invention of Sørensen was the pH scale.

The measurement was originally used by the Danish biochemist S.P.L. Sørensen to represent the
hydrogen ion concentration, expressed in equivalents per litre, of an aqueous solution: pH =
−log[H+] (in expressions of this kind, enclosure of a chemical symbol within
square brackets denotes that the concentration of the symbolized species is the quantity being
considered).

A pH meter is used to determine the acidity or alkalinity of the solution. pH is the concentration
of hydrogen ions in the solution. A solution containing more H + ions remains acidic while the
solution containing more OH- ions remains alkaline. pH value of solutions range from 1 to 14.

The solution having pH value 1 will be the highly acidic and with pH value 14 will be highly
basic. The acidity and alkalinity of any solution depend upon the concentration of hydrogen ions
(H+) and hydroxyl ions (OH-) respectively. A neutral solution as pure water has pH 7.
Solutions having the value of pH equal to 0 are known to be strongly acidic solutions. Further,
the acidity decreases as the value of pH increases from 0 to 7 whereas, solutions with the value
of pH equal to 14 are termed as strongly basic solutions.

The basicity decreases as the value of pH decreases from 14 to 7. The strength of acids and
bases depends on the number of H+ and OH– ions produced. Acids furnishing more number of
H+ ions are known to be strong acids and vice versa.

The degree of ionisation of acids and bases differ for different acids and bases. It helps in the
determination of the strength of acids and bases. The strength of an acid depends on the
concentration of hydronium ion (H3O+) too. With the help of the comparison between the
concentration of hydronium ion and the hydroxyl ion, we can distinguish between acids and
bases.

 For acidic solution: [H3O+] > [OH–]

 For neutral solution: [H3O+] = [OH–]

 For basic solution: [H3O+] < [OH–]

pH Value and Nature of a Solution

 If [H+] > 10-7, pH is less than 7 and the solution is acidic.

 If [H+] = 10-7, pH is 7 and the solution is neutral.

 If [H+] < 10-7, pH is more than 7 and the solution is basic.

Importance of pH

 Only a narrow range of pH change can be sustained by a living organism, any further
change in pH can make the living difficult. For example: in the case of acid rain, the pH
of water is less than 7. As it flows into a river, it lowers the pH of river water which
makes the survival of aquatic life difficult.

 We know that our stomach contains hydrochloric acid which helps in the digestion of
food. When the stomach produces too much of hydrochloric acid during indigestion, we
 feel a lot of pain and irritation. Hence, we generally use antacids or a mild base which
increases the pH of the acidic stomach and thus decreases the pain.

 Bacteria present in our mouth sometimes lower the pH of our mouth by producing acids
through degradation of the food particle. Hence, we are instructed to clean our mouths
with toothpaste (which are generally basic) to prevent their decay by maintaining the pH.

 We experience a lot of pain in case of bee-sting as the bee injects the methanoic acid
through its sting. Hence, we are generally advised to apply baking soda (Bicarbonate
Soda or Sodium hydrogen carbonate – NaHCO3) or other mild bases on the surface as it
helps in maintaining the pH of the surface.