General Chemistry Dr.

Wasan Taha

Acidosis and Alkalosis

ACIDS PRODUCED IN THE BODY
The following are the major sources of H+ (protons) production in the human
body.
• Carbonic acid (H2CO3): It is the chief acid produced in the body in the course of
oxidation in the cells. Oxidation of C-compounds resulting in CO2 production,
where about 10 to 20 or more moles being produced daily from oxidation of food
stuffs in the body. Approx. 300 litres of CO2 are produced and eliminated daily in
the body of an adult.
• Sulphuric acid (H2SO4): A strong dissociable acid produced during oxidation of
S-containing amino acids, e.g. cysteine/cystine and methionine.
• Phosphoric acid (H3PO4): Products of metabolism of dietary phosphoproteins,
nucleoproteins, phosphatides and hydrolysis of phosphoesters.
• Organic acids: Abnormal production and accumulation of certain intermediary
organic acids from oxidation of carbohydrates, fats and proteins, under certain
circumstances, e.g. pyruvic acid, lactic acid, acetoacetic acid, β-OH-butyric acid,
etc. Under ordinary conditions, PA/and LA and β-OH butyric acid are produced in
quantities of about 80 to 120 millimoles daily, which may increase considerably
under certain abnormal circumstances.
• Iatrogenic: Certain medicines like NH4Cl, mandelic acid, etc. may increase H+
concentration of blood when they are used as treatment, when administered in
excess.
Note: Although certain foodstuffs may provide a certain amount of potentially
“basic” substances, this is far exceeded by their potential acid content. Both the H +
ions and the anions produced by these acids must be disposed of.
Mechanisms of Regulation of pH
The mechanisms of regulation of blood pH involve the following factors:
(a) “Front-line” defence: They are mainly:
• Buffer systems in the blood: Which restrict pH change in body fluids.
• Respiratory mechanisms: Regulation of excretion of CO2 and hence, regulation
of H2CO3 concentration in EC fluid.

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(b) “Second-line” defence: This is achieved by kidneys (Renal mechanisms).

Ultimate excretion of excess of acid or base and thus ultimate regulation of
concentration of H+ and HCO3- ions in EC fluid.
(c) Dilution factor: The acids introduced into and formed in the body are
distributed throughout the ECF volume. Although this may not properly be
regarded as a regulatory mechanism, entrance of a given amount of acid into a
smaller volume of fluid, as in conditions of severe dehydration, results in
relatively greater rise in H+ ion concentration and decrease in effective buffer
base.
Most important buffer systems of blood are as follows:
Plasma buffers

Buffers of RB Cells

Role of Different Buffer Systems

1. Bicarbonate Buffer System (NaHCO3/H2CO3 = [Salt]/[Acid])
This consists of weak acid “Carbonic acid” (H2CO3) and its corresponding salt
with strong base (HCO3-), NaHCO3 (Sodium bicarbonate).

Normal ratio in blood = =

They are the chief buffers of blood and constitute the so called alkali reserve.
Neutralization of strong and non-volatile acids entering the ECF is achieved by the
bicarbonate buffers. Such acids, e.g. HCl, H2SO4, Lactic acid, etc. which are
strong and non-volatile react with NaHCO3 component.

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A strong and non-volatile acid is converted into weak (less dissociable) and
volatile acid at the expense of NaHCO3 (salt component of the buffer).
•H2CO3 thus formed, as it is volatile, is eliminated by diffusion of CO2 through
alveoli of lungs.
Note: Proper lung functioning is important.
Alkali reserve:
It is represented by the NaHCO3 concentration in the blood that has not yet
combined with strong and non-volatile acid. Normally, all acids except carbonic
acid react with bicarbonate to liberate CO2.
Strong, non-volatile acids + NaHCO3 → H2CO3 + Salt of acid LA, H2SO4, HCl,
etc.
H2CO3 ⇔ H2O + CO2 ↑
Advantages of bicarbonate buffer system:
Bicarbonate buffer system is efficient as compared to other buffer systems as:
• It is present in very high concentration than other buffer systems (26 to 28
millimole per litre).
• Produces H2CO3, which is a weak acid and volatile and CO2 is exhaled out.
• Hence, it is a very good physiological buffer and acts as a front line defence.
Disadvantage: As a chemical buffer, it is rather weak. pKa is further away from
the physiological pH.
2. Phosphate Buffer System
(Na2HPO4 / NaH2PO4 = [Alk PO4]/[Acid PO4])
Normal ratio in plasma is 4:1.
This ratio is kept constant with the help of the kidneys. Thus, phosphate buffer
system is directly linked up with the kidneys.
(a) When a strong acid enters the blood, it is fixed up by alkaline PO 4 (Na2HPO4)
which is converted to acid PO4. The acid PO4 (NaH2PO4) thus produced are
excreted by the kidneys, hence urine becomes more acidic.

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(b)When an alkali enters, it is buffered by the acid PO4, which is converted to

alkaline PO4 and is excreted in urine, producing increased alkalinity of urine.
Thus, phosphate buffer system works in conjunction with the kidneys. A normal
healthy kidney is necessary for proper functioning.
Disadvantage:
• Concentration in blood is low (1.0 millimole/ litre). So, as a physiological buffer
it is less efficient.
Advantage: As a chemical buffer it is very effective and better, as pka approaches
physiological pH.
3. Protein Buffer System
(Na+ Pr–/H+ Pr– = [Salt]/[Acid])
Buffering capacity of plasma proteins is much less than Hb. The latter operates
only in erythrocytes.
Example:
1. 1g of Hb binds 0.183 mEq of H+. On the other hand, 1g of plasma proteins
binds 0.110 mEq of H+, when titrated between pH 7.5 and 6.5.
2. Hb of 1L of blood as buffer can bind 27.5 mEq of H+. But plasma proteins
present in 1L of blood can buffer 4.24 mEq of H+ only between pH 7.5 and 6.5.
From the above examples, it is clear that Hb has more buffering capacity than
plasma proteins.
Buffering action of proteins
 In acidic medium: protein acts as a base, NH2 group takes up H+ ions from the
medium forming NH3+, proteins become +vely charged.
 In alkaline medium: Proteins act as an acid. Acidic COOH gr dissociates and
gives H+, forming COO–. H+ combines with OH– to produce a molecule of
water, proteins become –vely charged.

4. Hemoglobin as a Buffering Agent

With the pH range of 7.0 to 7.8, most of the physiological buffering action of Hb
is due to the “imidazole” group of amino acid “histidine”. Each molecule of Hb
contains 38 mols of Histidine. In α-chain, histidine at 87 position, and in β-chain,

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histidine at 92 position is directly linked with Fe++ of “haem”. Imidazole contains

two groups
1. Fe++ containing group which is concerned with carriage of O2, and
2. Imidazole N2 group, which can give up H+ (proton) and accept H+ depending
on the pH of the medium. Thus, buffering capacity of Hb is due to the presence of
“Imidazole” nitrogen group which remains dissociated in acidic medium and
conjugate base forms.
Acid-Base Imbalance
Carbonic acid is formed by dissolving carbon dioxide in aqueous body fluids. It is
a weak acid that ionizes to bicarbonate ion. The equation for these two equilibrium
reactions is as follows:
CO2 + H2O H2CO3 HCO3- + H+
Normally, in body fluids such as blood, there is 24 mEq/L of bicarbonate ion to 1.2
mEq/L of carbonic acid. The pH of the blood is within its normal range of 7.35-
7.45 when the ratio, 20 parts bicarbonate ion to 1 part carbonic acid, is maintained.
The pH of the blood becomes more acidic when the ratio [HCO3-]/[H2CO3]
becomes less than 20/1, say, 16/1, or 12/1. The acidic condition of the blood
signified by a pH less than 7.35 is called acidemia.
The pH of the blood becomes more basic when the ratio [HCO3-]/[H2CO3]
becomes greater than 20/1, say, 25/1, or 30/1. The alkaline condition of the blood
signified by a pH greater than 7.45 is called alkalemia.
Death occurs if the pH of the blood is more acidic than 6.8 or more basic than 7.8.
The effect on pH of a change in the ratio [HCO3-]/[H2CO3] is shown in Figure(1).

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We learned previously that all buffer solutions have a limited ability to withstand
additions of strong acids or bases without changing their pH very much. As soon as
the acid or its conjugate base is used up, the solution loses its ability to act as a
buffer. The buffers in the body are no exception to this rule. But buffers in the
body differ in one important respect from those in the laboratory. The body can
replenish components of the buffer solution as they are used up or can remove
from the body any excess component.
As an example, consider how the body uses the carbonic acid-bicarbonate ion
buffer system to cope with an increase in either the acid or the base concentration
in the blood.
ACIDOSIS
First, consider a patient who has an illness that causes an increase in the
concentration of acidic products in the blood. The physiologic processes causing
acidemia are called acidosis. The acidic products react with bicarbonate ions to
produce carbonic acid. This causes a decrease in the ratio [HCO3-]/[H2CO3]. Unless
something is done to return this ratio to normal, acidosis will occur.
One of the functions of both the lungs and the kidneys is to maintain the pH of the
blood by replenishing the buffer components that are used up or removing any
excess components from the body. The circulation of air into and out of the lungs,
called ventilation, produces the quickest response. An increase in the amount of
carbonic acid in the blood causes a corresponding increase in the amount of carbon

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dioxide formed from the decomposition of carbonic acid. To lose this excess
carbon dioxide, deeper and faster breathing, called hyperventilation occurs.
This causes a decrease in the acidity of the blood because the carbon dioxide
formed is lost through the lungs. If this does not return the pH to normal, the
kidneys can help by releasing more bicarbonate ion into the blood and removing
hydrogen ions. In these ways, the body tries to return the [HCO3-]/[H2CO3] ratio to
its normal value of 20 and maintain the acid-base balance in the blood.

ALKALOSIS
Consider a patient who has an illness that causes an increase in the concentration
of basic products in the blood. The physiologic processes causing alkalemia are
called alkalosis.
The lungs and the kidneys are equally well equipped to handle an increase of basic
products in the blood. These basic products react with carbonic acid to form
bicarbonate ions. This time the ratio [HCO3-]/[H2CO3] increases. The simplest way
to prevent this ratio from increasing is to conserve the carbon dioxide in the body
and use it to produce more carbonic acid. To do this, loss of carbon dioxide

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through the lungs is minimized by slower and shallow breathing, called

hypoventilation.
The kidneys can help if needed. But this time, bicarbonate ions are removed and
hydrogen ions are added to the blood. Thus, the lungs and kidneys can function to
maintain the pH of the blood within its normal range of 7.35-7.45.

Differentiation of metabolic acidosis and respiratory acidosis:

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General Chemistry Dr. Wasan Taha

Differentiation of metabolic alkalosis and respiratory alkalosis: